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1. Biallelic GGGCC repeat expansion leading to NAXE-related mitochondrial encephalopathy

Author

Kokoro Ozaki, Yukiko Yatsuka, Yoshinobu Oyazato, Atsushi Nishiyama, Kazuhiro R. Nitta, Yoshihito Kishita, Takuya Fushimi, Masaru Shimura, Shohei Noma, Yohei Sugiyama, Michihira Tagami, Moe Fukunaga, Hiroko Kinoshita, Tomoko Hirata, Wataru Suda, Yasuhiro Murakawa, Piero Carninci, Akira Ohtake, Kei Murayama, and Yasushi Okazaki

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Repeat expansions cause at least 50 hereditary disorders, including Friedreich ataxia and other diseases known to cause mitochondrial dysfunction. We identified a patient with NAXE-related mitochondrial encephalopathy and novel biallelic GGGCC repeat expansion as long as ~200 repeats in the NAXE promoter region using long-read sequencing. In addition to a marked reduction in the RNA and protein, we found a marked reduction in nascent RNA in the promoter using native elongating transcript-cap analysis of gene expression (NET-CAGE), suggesting transcriptional suppression. Accordingly, CpG hypermethylation was observed in the repeat region. Genetic analyses determined that homozygosity in the patient was due to maternal chromosome 1 uniparental disomy (UPD). We assessed short variants within NAXE including the repeat region in the undiagnosed mitochondrial encephalopathy cohort of 242 patients. This study identified the GGGCC repeat expansion causing a mitochondrial disease and suggests that UPD could significantly contribute to homozygosity for rare repeat-expanded alleles.

Published
2024
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2. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Mathys Grapotte, Manu Saraswat, Chloé Bessière, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-Ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, FANTOM consortium, Clément Chatelain, Piero Carninci, Michiel J. L. de Hoon, Wyeth W. Wasserman, Laurent Bréhélin, and Charles-Henri Lecellier

Subjects
Science
Abstract

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Published
2021
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3. Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter

Author

Yosuke Ito, Yasuhisa Terao, Shohei Noma, Michihira Tagami, Emiko Yoshida, Yoshihide Hayashizaki, Masayoshi Itoh, and Hideya Kawaji

Subjects
Medicine, Science
Abstract

Abstract Gene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells.

Published
2021
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4. Author Correction: Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Mathys Grapotte, Manu Saraswat, Chloé Bessière, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-Ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, FANTOM consortium, Clément Chatelain, Piero Carninci, Michiel J. L. de Hoon, Wyeth W. Wasserman, Laurent Bréhélin, and Charles-Henri Lecellier

Subjects
Science
Published
2022
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6. Effects of the turn-back primer on intermediate product generation in isothermal DNA amplification

Author

Yuki Tanaka, Yasumasa Kimura, Yasumasa Mitani, Yuki Kawai, Alexander Lezhava, Shohei Noma, Michihira Tagami, Jun Kawai, Yoshihide Hayashizaki, and Kengo Usui

Subjects
isothermal DNA amplification, strand displacement, turn-back primer, single-molecule amplification, 454 sequencing, Biology (General), QH301-705.5
Abstract

In DNA amplification, the initial step of copying a target sequence from the template DNA, or the so-called intermediate product generation step, is very important. In examining the turn-back primer (TP)–dependent isothermal DNA amplification (TIA) method, we determined the actual time point of intermediate product generation by extrapolating dsDNA amplification curves. Our results indicate that intermediate product creation is the rate-limiting step in TIA, and good TP design is advantageous for improving the intermediate production process.

Published
2010
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7. A promoter-level mammalian expression atlas.

Author

The Fantom Consortium, RIKEN PMII, RIKEN CLST (DGT), Alistair R. R. Forrest, Hideya Kawaji, Michael Rehli, J. Kenneth Baillie, Michiel J. L. de Hoon, Vanja Haberle, Timo Lassmann, Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J. Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. M. Semple, Yuri Ishizu, Robert S. Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M. Altschuler, Takahiro Arakawa, John A. C. Archer, Peter Arner, Magda Babina, Sarah Rennie, Piotr J. Balwierz, Anthony G. Beckhouse, Swati Pradhan-Bhatt, Judith A. Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A. Maxwell Burroughs, Andrea Califano, Carlo V. Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans Clevers, Emiliano Dalla, Carrie A. Davis, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S. B. Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach-Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E. Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun-ichi Furusawa, Teunis B. Geijtenbeek, Andrew P. Gibson, Thomas R. Gingeras, Daniel Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J. Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J. Hitchens, Shannan J. Ho Sui, Oliver M. Hofmann, Ilka Hoof, Fumi Hori, Lukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R. Jankovic, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Kanamori-Katayama, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I. Kawamura, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T. Kwon, Jeroen F. J. Laros, Weonju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan Mackay-Sim, Ri-ichiroh Manabe, Jessica Cara Mar, Benoit Marchand, Anthony Mathelier, Niklas Mejhert, Alison M. Meynert, Yosuke Mizuno, David A. de Lima Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine Mummery, Mitsuyoshi Murata, Sayaka Nagao-Sato, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James G. D. Prendergast, Owen J. L. Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten B. Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Hironori Sato, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik A. Schultes, Gundula G. Schulze-Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf K. Swoboda, Peter A. C. 't Hoen, Michihira Tagami, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson 0002, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda M. van den Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Susan E. Zabierowski, Peter G. Zhang, Xiaobei Zhao, Silvia Zucchelli, Kim M. Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajic, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David A. Hume, Piero Carninci, and Yoshihide Hayashizaki

Published
2014
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8. Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter

Author

Masayoshi Itoh, Yoshihide Hayashizaki, Emiko Yoshida, Shohei Noma, Hideya Kawaji, Michihira Tagami, Yosuke Ito, and Yasuhisa Terao

Subjects
Gynaecological cancer, Gene isoform, Multidisciplinary, Molecular biology, Science, Locus (genetics), Amplicon, Biology, Article, Exon, Transcription (biology), Complementary DNA, Gene expression, Medicine, Nanopore sequencing
Abstract

Gene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells.

Published
2021

9. Comparative transcriptomics of primary cells in vertebrates

Author

Hideya Kawaji, Imad Abugessaisa, Takeya Kasukawa, Luigi Marchionni, Jessica Severin, Martin S. Taylor, Shohei Noma, Erik Arner, Robin Andersson, Yoshihide Hayashizaki, Akira Hasegawa, Tanvir Alam, Levon M. Khachigian, Hiroshi Tarui, Michiel J. L. de Hoon, Saumya Agrawal, Piero Carninci, Yuri Ishizu, Robert Young, Guojun Sheng, Timo Lassmann, Masayoshi Itoh, Marina Lizio, Jordan A. Ramilowski, and Alistair R. R. Forrest

Subjects
Biology, Evolution, Molecular, Transcriptome, Mice, 03 medical and health sciences, Dogs, 0302 clinical medicine, Species Specificity, Gene expression, Genetics, Transcriptional regulation, Animals, Humans, Gene Regulatory Networks, Nucleotide Motifs, Promoter Regions, Genetic, Enhancer, Gene, Genetics (clinical), 030304 developmental biology, Principal Component Analysis, 0303 health sciences, Research, Gene Expression Profiling, Promoter, Phenotype, Rats, Gene expression profiling, MicroRNAs, Chickens, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have diverged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that divergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.

Published
2020
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10. High quality genome assembly of the anhydrobiotic midge provides insights on a single chromosome-based emergence of extreme desiccation tolerance

Author

Yuki Yoshida, Nurislam Shaikhutdinov, Olga Kozlova, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Hiromi Nishiyori-Sueki, Miki Kojima-Ishiyama, Shohei Noma, Alexander Cherkasov, Guzel Gazizova, Aigul Nasibullina, Ruslan Deviatiiarov, Elena Shagimardanova, Alina Ryabova, Katsushi Yamaguchi, Takahiro Bino, Shuji Shigenobu, Shoko Tokumoto, Yugo Miyata, Richard Cornette, Takahiro G Yamada, Akira Funahashi, Masaru Tomita, Oleg Gusev, and Takahiro Kikawada

Subjects
fungi
Abstract

Non-biting midges (Chironomidae) are known to inhabit a wide range of environments, and certain species can tolerate extreme conditions, where the rest of insects cannot survive. In particular, the sleeping chironomid Polypedilum vanderplanki is known for the remarkable ability of its larvae to withstand almost complete desiccation by entering a state called anhydrobiosis. Chromosome numbers in chironomids are higher than in other dipterans and this extra genomic resource might facilitate rapid adaptation to novel environments. We used improved sequencing strategies to assemble a chromosome-level genome sequence for P. vanderplanki for deep comparative analysis of genomic location of genes associated with desiccation tolerance. Using whole genome-based cross-species and intra-species analysis, we provide evidence for the unique functional specialization of Chromosome 4 through extensive acquisition of novel genes. In contrast to other insect genomes, in the sleeping chironomid a uniquely high degree of subfunctionalization in paralogous anhydrobiosis genes occurs in this chromosome, as well as pseudogenization in a highly duplicated gene family. Our findings suggest that the Chromosome 4 in Polypedilum is a site of high genetic turnover, allowing it to act as a ‘sandbox’ for evolutionary experiments, thus facilitating the rapid adaptation of midges to harsh environments.

Published
2021

11. Publisher Correction: Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter

Author

Yoshihide Hayashizaki, Yosuke Ito, Shohei Noma, Yasuhisa Terao, Michihira Tagami, Hideya Kawaji, Emiko Yoshida, and Masayoshi Itoh

Subjects
Gene isoform, Science, media_common.quotation_subject, Locus (genetics), Biology, Tumor Cells, Cultured, Humans, Protein Isoforms, RNA, Messenger, Promoter Regions, Genetic, media_common, Genetics, Multidisciplinary, Tumor Suppressor Proteins, TACC2, Exons, Publisher Correction, Introns, Endometrial Neoplasms, Alternative Splicing, Medicine, Female, Nanopore sequencing, Carrier Proteins, Diversity (politics)
Abstract

Gene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells.

Published
2021
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13. Morphology of the respiratory vasculature of the mudskipper Boleophthalmus pectinirostris (Gobiidae: Oxudercinae)

Author

Atsushi Ishimatsu, Shohei Noma, and Mariko Kurita

Subjects
Gill, Gills, biology, Fishes, Anatomy, Arteries, biology.organism_classification, Microcirculation, Perciformes, Veins, Major duodenal papilla, Mudskipper, medicine.anatomical_structure, Arteriole, medicine.artery, Circulatory system, medicine, Animals, Animal Science and Zoology, Respiratory system, Developmental Biology, Artery
Abstract

The gross morphology of the circulatory system in the amphibious mudskipper, Boleophthalmus pectinirostris, conforms with the typical teleost configuration, in which gills and systemic vascular beds are connected in series. However, at the microscopic level, the vasculatures of the respiratory organs, the inner epithelium of the bucco-opercular cavity, gills and skin, all show specializations for aerial gas exchange. The epithelium of the bucco-opercular cavity is heavily vascularized by respiratory capillaries that are derived from systemic arteries of the head, mainly branches of the hyomandibular artery and the dorsal opercular artery. The respiratory circuit of the secondary lamellae of the gills consists of 15-17 channels running in parallel, unlike the lacuna-like blood space of aquatic fishes. The most notable specialization is found in the microcirculation of the respiratory papillae in the skin. Each respiratory papilla is supplied by an arteriole that is derived from a systemic artery, mainly the cranial artery in the head and the segmental artery in the trunk. The arteriole divides several times along its course to the apical region of a papilla, where the branches split into approximately 65 capillaries that radiate to the periphery of the papilla. The capillaries twist 5-10 times before they unite to form the venules that encircle maximally half the circumference of a papilla. A variable number of venules merge into a vein, which progressively coalesces with veins from other papillae. There is no morphological specialization that separates oxygen-rich effluent blood of the epithelia of the bucco-opercular cavity and the respiratory papillae of the skin from the oxygen-poor systemic venous blood. The ecophysiological implications of these findings are discussed in relation to the environmental conditions that B. pectinirostris experience during tidal cycles in the warm months and during overwintering.

Published
2021

14. Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation

Author

Rei Yoshimoto, Jagat K. Chhipi-Shrestha, Daisuke Kaida, Shinichi Nakagawa, Harukazu Suzuki, A. Maxwell Burroughs, Masaaki Furuno, Shintaro Iwasaki, Tilman Schneider-Poetsch, Akila Mayeda, Shohei Noma, Minoru Yoshida, and Yoshihide Hayashizaki

Subjects
Polyadenylation, RNA Splicing, Clinical Biochemistry, Biology, Biochemistry, Ribonucleoprotein, U1 Small Nuclear, Drug Discovery, Gene expression, Tumor Cells, Cultured, Humans, snRNP, Spiro Compounds, Nuclear export signal, Molecular Biology, Pyrans, Pharmacology, Small Nuclear Ribonucleoprotein Particle, Intron, RNA, Phosphoproteins, Cell biology, RNA splicing, Molecular Medicine, Female, RNA, Long Noncoding, RNA Splicing Factors, HeLa Cells
Abstract

RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our understanding of the interaction between splicing and other RNA regulatory mechanisms remains incomplete. Moreover, the impact of chemical splicing inhibition on long non-coding RNAs (lncRNAs) has been poorly understood. Here, we demonstrate that spliceostatin A (SSA), a chemical splicing modulator that binds to the SF3B subcomplex of the U2 small nuclear ribonucleoprotein particle (snRNP), limits U1 snRNP availability in splicing, resulting in premature cleavage and polyadenylation of MALAT1, a nuclear lncRNA, as well as protein-coding mRNAs. Therefore, truncated transcripts are exported into the cytoplasm and translated, resulting in aberrant protein products. Our work demonstrates that active recycling of the splicing machinery maintains homeostasis of RNA processing beyond intron excision.

Published
2020

15. Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A

Author

Yumi Kawamura, Daisuke Kaida, Minoru Yoshida, Masaaki Furuno, A. Maxwell Burroughs, Akila Mayeda, Shohei Noma, Rei Yoshimoto, Harukazu Suzuki, and Yoshihide Hayashizaki

Subjects
0301 basic medicine, Cytoplasm, Spliceosome, RNA Splicing, Biology, Article, 03 medical and health sciences, Neoplasms, RNA Precursors, medicine, Humans, Spiro Compounds, snRNP, Molecular Biology, Pyrans, Cell Nucleus, Sequence Analysis, RNA, Intron, Subcellular localization, Cell biology, Gene Expression Regulation, Neoplastic, stomatognathic diseases, Cell nucleus, 030104 developmental biology, medicine.anatomical_structure, RNA splicing, Precursor mRNA, Cyclin-Dependent Kinase Inhibitor p27, HeLa Cells
Abstract

Spliceostatin A (SSA) is a methyl ketal derivative of FR901464, a potent antitumor compound isolated from a culture broth of Pseudomonas sp. no. 2663. These compounds selectively bind to the essential spliceosome component SF3b, a subcomplex of the U2 snRNP, to inhibit pre-mRNA splicing. However, the mechanism of SSA's antitumor activity is unknown. It is noteworthy that SSA causes accumulation of a truncated form of the CDK inhibitor protein p27 translated from CDKN1B pre-mRNA, which is involved in SSA-induced cell-cycle arrest. However, it is still unclear whether pre-mRNAs are uniformly exported from the nucleus following SSA treatment. We performed RNA-seq analysis on nuclear and cytoplasmic fractions of SSA-treated cells. Our statistical analyses showed that intron retention is the major consequence of SSA treatment, and a small number of intron-containing pre-mRNAs leak into the cytoplasm. Using a series of reporter plasmids to investigate the roles of intronic sequences in the pre-mRNA leakage, we showed that the strength of the 5′ splice site affects pre-mRNA leakage. Additionally, we found that the level of pre-mRNA leakage is related to transcript length. These results suggest that the strength of the 5′ splice site and the length of the transcripts are determinants of the pre-mRNA leakage induced by SF3b inhibitors.

Published
2016
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16. FANTOM5 CAGE profiles of human and mouse samples

Author

Jun Kawai, Anthony G Beckhouse, Dipti Vijayan, Michael Rehli, Toshiyuki Nakamura, Yuki Hasegawa, Timothy C. Barnett, Hisashi Shimoji, Erik Arner, Masayoshi Itoh, Masahide Hamaguchi, Sarah Klein, Reto Guler, Patrizia Rizzu, Atsutaka Kubosaki, Soichi Kojima, Timo Lassmann, Kelly J. Morris, Mutsumi Kanamori-Katayama, Ri Ichiroh Manabe, Hiromasa Morikawa, Kelly J Hitchens, Fumi Hori, Linda M. van den Berg, Yasushi Okazaki, Andru Tomoiu, Antti Sajantila, Akiko Saka, Thierry Sengstag, Alessandro Bonetti, Haruhiko Koseki, Matthias Edinger, Mitsuhiro Ohshima, Carsten O. Daub, Jayson Harshbarger, Sachi Ishikawa-Kato, Tsugumi Kawashima, Christine L. Mummery, Niklas Mejhert, Jun Takai, Dan Goldowitz, Naoko Suzuki, Guojun Sheng, David A. Hume, Hiroshi Kawamoto, Ai Kaiho, Jun Ichi Furusawa, Ailsa J Carlisle, Tomokatsu Ikawa, Shiro Fukuda, Peter G. Zhang, Akira Hasegawa, James Briggs, Toshio Kitamura, Alistair R. R. Forrest, Takahiro Arakawa, Marcvande Wetering, Shohei Noma, Fumio Nakahara, Jessica Severin, Sven Guhl, Atsushi Kondo, Mary C. Farach-Carson, Hans Clevers, Afsaneh Eslami, Christian Schmidl, Peter Heutink, Hideki Tatsukawa, Anita Schwegmann, Noriko Ninomiya, Antje Blumenthal, Yoshihide Hayashizaki, Suzana Savvi, Thomas J. Ha, Claudio Schneider, Daisuke Sugiyama, Hironori Satoh, Mitsuru Morimoto, Hiroki Sato, Yosuke Mizuno, Meenhard Herlyn, Hozumi Motohashi, Shigehiro Yoshida, Hiroo Toyoda, Christophe Simon, Piero Carninci, Tadasuke Nozaki, Hideya Kawaji, Louise N. Winteringham, Swati Pradhan-Bhatt, Imad Abugessaisa, Michihira Tagami, Tony J. Kenna, Yoko Yamaguchi, Geoffrey J. Faulkner, Alka Saxena, Naoto Kondo, Dmitry A. Ovchinnikov, Rie Fujita, Ernst J. Wolvetang, Michael Detmar, Miki Kojima, Peter Arner, Mitsuko Hara, Stefano Gustincich, Carrie A. Davis, Judith S. Kempfle, Margaret Patrikakis, Alan Mackay-Sim, Carmelo Ferrai, Yutaka Nakachi, Juha Kere, Mitsuyoshi Murata, Shimon Sakaguchi, Soichi Ogishima, Silvia Zucchelli, Andreas Lennartsson, Thomas R. Gingeras, Masanori Suzuki, Beatrice Bodega, Sugata Roy, Sayaka Nagao-Sato, Mitsuhiro Endoh, Anna Ehrlund, J Kenneth Baillie, Mizuho Sakai, Michela Fagiolini, Taeko Dohi, Christine A. Wells, Frank Brombacher, Masayuki Yamamoto, Robert Passier, Lynsey Fairbairn, Teunis B. H. Geijtenbeek, Shigeo Koyasu, Hiromi Nishiyori-Sueki, Yuri Ishizu, Yuki I. Kawamura, Chiyo Yanagi-Mizuochi, Roberto Verardo, Misako Yoneda, Mariko Okada-Hatakeyama, Kaoru Kaida, Ana Pombo, Gundula Schulze-Tanzil, Lesley M. Forrester, Kim M. Summers, Harukazu Suzuki, Naganari Ohkura, Weon Ju Lee, Hiroshi Tanaka, Alan J. Knox, Karl Ekwall, Yukio Nakamura, Serkan Sahin, Shuhei Noguchi, Hiroshi Ohno, Yohei Yonekura, Richard A Axton, Marina Lizio, S. Peter Klinken, Malcolm E. Fisher, Shoko Watanabe, Magda Babina, Xian-Yang Qin, Takaaki Sugiyama, B. Albert S. Edge, Eri Saijyo, Valerio Orlando, Takeya Kasukawa, Kazuyo Moro, Kenichi Nakazato, Naoko Takahashi, Levon M. Khachigian, Chieko Kai, Masaaki Furuno, Jay W. Shin, Hideki Enomoto, Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Infectious diseases, Infectious diseases, and AII - Amsterdam institute for Infection and Immunity

Subjects
0301 basic medicine, 500 Naturwissenschaften und Mathematik::570 Biowissenschaften, Biologie, Data Descriptor, Molecular biology, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Genome, Mice, 0302 clinical medicine, Transcription (biology), Promoter Regions, Genetic, Non-U.S. Gov't, Regulation of gene expression, Research Support, Non-U.S. Gov't, Statistics, Computer Science Applications1707 Computer Vision and Pattern Recognition, Computer Science Applications, Library and Information Sciences, Information Systems, Statistics, Probability and Uncertainty, Statistics and Probability, ddc:500, Cell activation, Systems biology, Cell biology, Computational biology, Biology, Research Support, Education, 03 medical and health sciences, Species Specificity, Developmental biology, Journal Article, Animals, Humans, Enhancer, Gene Expression Profiling, Promoter, Cap analysis gene expression, Computational biology and bioinformatics, Gene expression profiling, 030104 developmental biology, Gene Expression Regulation, Cardiovascular and Metabolic Diseases, Probability and Uncertainty, 030217 neurology & neurosurgery
Abstract

Scientific Data, 4, ISSN:2052-4463

Published
2017
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17. An atlas of human long non-coding RNAs with accurate 5′ ends

Author

Yukio Nakamura, Mickal Mendez, Julian Gough, Jessica Severin, Owen J. L. Rackham, Dave Tang, A. Maxwell Burroughs, Masayoshi Itoh, Timo Lassmann, Carsten O. Daub, Leonard Lipovich, Erik Arner, Yoshihide Hayashizaki, Sarah Djebali, Soichi Kojima, Magda Babina, Shohei Noma, Piero Carninci, Hideya Kawaji, Sebastian Schmeier, Peter Heutink, Yulia A. Medvedeva, Tanvir Alam, Alison C. Testa, Elena Denisenko, Marina Lizio, Christine A. Wells, Chi Wai Yip, Akira Hasegawa, Jordan A. Ramilowski, Alistair R. R. Forrest, Michiel J. L. de Hoon, Harukazu Suzuki, Takeya Kasukawa, Nicolas Bertin, Thomas M. Poulsen, Imad Abugessaisa, Jayson Harshbarger, Chung-Chau Hon, Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Omics Sci Ctr, Tsurumi Ku, Ctr Translat Med, Canc Sci Inst Singapore, National University of Singapore (NUS), Human Longev Singapore Pte Ltd, Dept Comp Sci, Life Sci, University of Bristol [Bristol], Cardiovasc & Metab Disorders, Duke-NUS Medical School [Singapore], Inst Nat & Math Sci, Biotechnol Res Inst Drug Discovery BRD, Natl Inst Adv Ind Sci & Technol, Prevent Med & Diag Innovat Program, Natl Lib Med, Natl Ctr Biotechnol Informat, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ctr Gen Regulat CRG, Barcelona Institute of Science and Technology (BIST), Universitat Pompeu Fabra [Barcelona] (UPF), Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, King Abdullah University of Science and Technology (KAUST), Biotechnol Res Ctr, Inst Bioengn, the Russian Academy of Sciences [Moscow, Russia] (RAS), Vavilov Inst Gen Genet, Russian Academy of Sciences [Moscow] (RAS), QEII Med Ctr, Harry Perkins Inst Med Res, The University of Western Australia (UWA), Med Res Ctr, Ctr Mol Med & Genet, Wayne State University [Detroit], Sch Med, Dept Neurol, Dept Comp Sci, North Dakota State University (NDSU), Telethon Kids Inst, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dept Dermatol & Allergy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Australian Inst Bioengn & Nanotechno, University of Queensland [Brisbane], Fac Med, Dept Anat & Neurosci, University of Melbourne, CLST Div Biofunct Dynam Imaging, BioResource Ctr, Cell Engn Div, Université de Tsukuba = University of Tsukuba, Dept Biosci & Nutr, Karolinska Institute, QEII Med Ctr, Harry Perkins Inst Med Re, Duke NUS Medical School, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Universitat Pompeu Fabra [Barcelona], Russian Academy of Sciences, Wayne State University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, and University of Tsukuba

Subjects
0301 basic medicine, RNA Stability, [SDV]Life Sciences [q-bio], genetics [Transcriptome], Datasets as Topic, genetics [RNA, Long Noncoding], Genome, Epigenesis, Genetic, 0302 clinical medicine, Databases, Genetic, Promoter Regions, Genetic, Cells, Cultured, Conserved Sequence, Genetics, Regulation of gene expression, Multidisciplinary, genetics [Organ Specificity], Genomics, Enhancer Elements, Genetic, annotation, Organ Specificity, 030220 oncology & carcinogenesis, RNA, Long Noncoding, ddc:500, pr interval, transcription, architecture, Quantitative Trait Loci, Biology, Polymorphism, Single Nucleotide, Article, genetics [RNA, Messenger], 03 medical and health sciences, seq, evolution, genetics [Conserved Sequence], Humans, genetics [Genome, Human], RNA, Messenger, Gene, Internet, genetics [Quantitative Trait Loci], Genome, Human, Gene Expression Profiling, genetics [Enhancer Elements, Genetic], Molecular Sequence Annotation, landscape, gene-expression, Cap analysis gene expression, promoter usage, Gene expression profiling, chemistry [RNA, Long Noncoding], 030104 developmental biology, Gene Expression Regulation, genetics [Promoter Regions, Genetic], Expression quantitative trait loci, genome-wide association, Human genome, Transcriptome, Genome-Wide Association Study
Abstract

Long non-coding RNAs (lncRNAs) are largely heterogeneous and functionally uncharacterized. Here, using FANTOM5 cap analysis of gene expression (CAGE) data, we integrate multiple transcript collections to generate a comprehensive atlas of 27,919 human lncRNA genes with high-confidence 5' ends and expression profiles across 1,829 samples from the major human primary cell types and tissues. Genomic and epigenomic classification of these lncRNAs reveals that most intergenic lncRNAs originate from enhancers rather than from promoters. Incorporating genetic and expression data, we show that lncRNAs overlapping trait-associated single nucleotide polymorphisms are specifically expressed in cell types relevant to the traits, implicating these lncRNAs in multiple diseases. We further demonstrate that lncRNAs overlapping expression quantitative trait loci (eQTL)-associated single nucleotide polymorphisms of messenger RNAs are co-expressed with the corresponding messenger RNAs, suggesting their potential roles in transcriptional regulation. Combining these findings with conservation data, we identify 19,175 potentially functional lncRNAs in the human genome.

Published
2017
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18. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

Author

Albin Sandelin, Takashi Gojobori, Timo Lassmann, Hiroshi Asahara, Claes Wahlestedt, Lukasz Huminiecki, Georges St. Laurent, Yoshinari Ando, Takehiro Hashimoto, Denis C. Bauer, Ariel S. Schwartz, Pär G. Engström, Michael Rehli, Hiromi Nishiyori, Katharine M. Irvine, Andreas Lennartsson, Susanne Heinzel, Yoichi Takenaka, Ole Winther, Nicole Cloonan, Megumi Hashimoto, Winston Hide, Takuma Sano, Boris Lenhard, Michiel J. L. de Hoon, Sarah A. Teichmann, Timothy Ravasi, Naoko Imamoto, Ryoko Ishihara, Syuhei Kimura, Mariko Hatakeyama, Yusuke Inoue, Joe Chiba, Shizu Takeda, Linda Wu, Julian Gough, John Quackenbush, Miho Sera, Yasumasa Kimura, Vladimir B. Bajic, Frank Brombacher, Kazumi Yamaguchi, Toshitsugu Okayama, David Fredman, Hideya Kawaji, Colin A. Semple, Ryan J. Taft, Cas Simons, Ko Fujimori, Masaaki Furuno, Andrew Waterhouse, Ajit Kumar, Jesper Tegnér, Tsugumi Kawashima, Nikolai Petrovsky, J. Lynn Fink, Michihira Tagami, Jun Otomo, Etsuko Miyamoto-Sato, Shiro Fukuda, Cameron Ross MacPherson, Shintaro Katayama, Erika Bulger, Toshio Kojima, Alistair R. R. Forrest, Anders Jacobsen, Yasushi Okazaki, Rohan D. Teasdale, Chikatoshi Kai, Johan Björkegren, Takahiro Suzuki, Carsten O. Daub, Christian Schönbach, Miki Kojima, Sebastian Schmeier, Alistair M. Chalk, Hiroaki Kitano, Sanne Nygaard, Kazuhiko Nakabayashi, Kai Tan, Yasuhiro Tomaru, Noriko Ninomiya, Piotr J. Balwierz, Marina Lizio, Altuna Akalin, Maki Asada, Norihiro Maeda, Satoshi Inoue, Takahiro Arakawa, Shohei Noma, Adam Dawe, Michael Hörnquist, Mika Gustafsson, Stuart Meier, Sei Miyamoto, Ryuichiro Kimura, Takeshi Konno, Kate Schroder, Christine A. Wells, Kazunori Waki, Christopher G. Maher, Nicolas Bertin, Ai Kaiho, Chihiro Ogawa, Shinji Kondo, Mika Nakano, Sean M. Grimmond, Matthew J. Sweet, Jun Yasuda, Aleksandar Radovanovic, Valerio Orlando, Yukari Takahashi, Mihaela Zavolan, Jessica Severin, Markus C. Kerr, Anders Krogh, Hiroshi Yanagawa, Hisashi Miura, John S. Mattick, Eivind Valen, Josée Dostie, Magbubah Essack, Monique Maqungo, Haruka Okuda-Yabukami, Oliver Hofmann, Anthony G Beckhouse, Rintaro Saito, Yutaka Nakachi, Yuki Hasegawa, Masanori Suzuki, Mitsuyoshi Murata, Harukazu Suzuki, Nicholas Matigian, Takao Iwayanagi, Hisashi Koga, Jun Kawai, Hideo Matsuda, Charles Plessy, Mikhail Pachkov, Kengo Imamura, Morten Lindow, Yayoi Kitazume, Erik Arner, Kazuho Ikeo, Yoshihide Hayashizaki, Timothy L. Bailey, Geoffrey J. Faulkner, Martin S. Taylor, Mutsumi Kanamori-Katayama, Mandeep Kaur, Christophe Simon, Piero Carninci, Atsutaka Kubosaki, Chika Kawazu, Katsuhiko Shirahige, Adele Kruger, Jessica C. Mar, Kayoko Murakami, David A. Hume, and Erik van Nimwegen

Subjects
Transcription, Genetic, Cellular differentiation, Molecular Sequence Data, Gene regulatory network, Biology, Bioinformatics, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Serum response factor, Genetics, Humans, Gene Regulatory Networks, RNA, Small Interfering, Promoter Regions, Genetic, Transcription factor, 030304 developmental biology, Cell Proliferation, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Base Sequence, Models, Genetic, Gene Expression Profiling, Pioneer factor, Myeloid leukemia, Cell Differentiation, Cell biology, Gene expression profiling, Leukemia, Myeloid, 030220 oncology & carcinogenesis
Abstract

Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.

Published
2009
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19. Expression of Golgi Membrane Protein p138 is Cell Cycle-independent and Dissociated from Centrosome Duplication

Author

Shohei Noma, Hideki Goko, Tatsuo Yagura, Fumiaki Yamao, and Kohei Doi

Subjects
G2 Phase, Cell division, Physiology, Vesicular Transport Proteins, Golgi Apparatus, Mitosis, S Phase, symbols.namesake, Protein biosynthesis, Humans, Topoisomerase II Inhibitors, Centrosome duplication, RNA, Messenger, Molecular Biology, Secretory pathway, Cell Size, Etoposide, Nucleic Acid Synthesis Inhibitors, Centrosome, Hybridomas, Membrane Glycoproteins, Chemistry, Cell Cycle, Membrane Proteins, Cell Biology, General Medicine, Cell plate, Golgi apparatus, Cell cycle, Flow Cytometry, Phosphoproteins, Cell biology, symbols, Thymidine
Abstract

In order to elucidate the mechanism controlling the biogenesis of the Golgi complex, we have studied whether the expression of a resident membrane protein p138 of the Golgi complex is dependent upon the cell cycle. The protein level of p138 in human KB cells was increased during thymidine block to synchronize the cells in the early-S phase, but changed little from S to G2 after release from the block. On the other hand, the mRNA level of the p138 gene was constant during the block. The change in mRNA level in the cells was small with a low peak at S to G2. Both p138 protein and mRNA levels decreased after cell division and then rose rapidly to the same level as those of log-phase cells in the next G1 to S. Thus, translation of p138 protein was upregulated in the cells at the early-S phase. However, we found also that the p138 protein level increased during an arrest at G2/M caused by etoposide. The kinetics of centrosome duplication apparently differ from those of p138 protein production. The duplication occurred mainly at S to G2 after the release from thymidine block, while the ratio of cells containing duplicated centrosomes increased gradually during the block. Taken together, these results show that both the translation and transcription of p138 protein are regulated independent of the cell cycle and dissociated from the duplication of the centrosome. Rather, the expression of p138 protein seems to be coupled with a change in cell size since both thymidine block and etoposide inhibition resulted in an apparent increase in cell size.

Published
2002
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20. Effects of the turn-back primer on intermediate product generation in isothermal DNA amplification

Author

Alexander Lezhava, Yoshihide Hayashizaki, Yuki Tanaka, Yasumasa Mitani, Michihira Tagami, Shohei Noma, Yasumasa Kimura, Kengo Usui, Yuki Kawai, and Jun Kawai

Subjects
Models, Molecular, Models, Genetic, Sequence Analysis, DNA, Biology, Dna amplification, Combinatorial chemistry, Molecular biology, General Biochemistry, Genetics and Molecular Biology, Intermediate product, Isothermal process, Turn (biochemistry), Nucleic Acid Probes, Humans, Primer (molecular biology), Nucleic Acid Amplification Techniques, Algorithms, Biotechnology, DNA Primers
Abstract

In DNA amplification, the initial step of copying a target sequence from the template DNA, or the so-called intermediate product generation step, is very important. In examining the turn-back primer (TP)–dependent isothermal DNA amplification (TIA) method, we determined the actual time point of intermediate product generation by extrapolating dsDNA amplification curves. Our results indicate that intermediate product creation is the rate-limiting step in TIA, and good TP design is advantageous for improving the intermediate production process.

Published
2010

21. A promoter-level mammalian expression atlas

Author

Frank Brombacher, Wyeth W. Wasserman, Hiromasa Morikawa, Fumi Hori, Sayaka Nagao-Sato, Artem S. Kasianov, Mitsuhiro Endoh, Ilka Hoof, Hans Clevers, Hideki Tatsukawa, Anita Schwegmann, Kang Li, David A. de Lima Morais, Yoshihide Hayashizaki, Morana Vitezic, Judith A. Blake, Leonard Lipovich, Hozumi Motohashi, Timothy Ravasi, Meenhard Herlyn, Shuji Kawaguchi, Antti Sajantila, Haruhiko Koseki, Lukasz Huminiecki, Tsugumi Kawashima, Carrie A. Davis, Mamoon Rashid, Winston Hide, Alka Saxena, Mizuho Sakai, Carsten O. Daub, Kim M. Summers, Yuki Hasegawa, Hisashi Shimoji, Margaret Patrikakis, Efthymios Motakis, Morten Beck Rye, Dan Goldowitz, Masaaki Furuno, Lynsey Fairbairn, Alan Mackay-Sim, Andreas Lennartsson, John A.C. Archer, Mitsuru Morimoto, Harukazu Suzuki, Silvia Zucchelli, Weon Ju Lee, Hiroki Sato, Alan J. Knox, Margherita Francescatto, Xiaobei Zhao, Jay W. Shin, Thomas R. Gingeras, Soichi Ogishima, Jayson Harshbarger, Mark Thompson, Beatrice Bodega, Marco Chierici, Shintaro Katayama, Albin Sandelin, Sarah Rennie, Silvano Piazza, Tomokatsu Ikawa, Matthias Harbers, Magda Babina, Peter G. Zhang, Gabriel M. Altschule, Lenhard Vladimir B. Bajic, Andrew P. Gibson, Malcolm E. Fisher, Karl Ekwall, Yukio Nakamura, Arnab Pain, Michiel J. L. de Hoon, Toshio Kitamura, Anthony G Beckhouse, Ai Kaiho, Julian Gough, James Briggs, Jordan A. Ramilowski, Miki Kojima, Alistair R. R. Forrest, Erik Anthony Schultes, Jessica C. Mar, Dipti Vijayan, Peter Arner, S. Peter Klinken, Michael Rehli, Kazuhiro Kajiyama, Christophe Simon, Piero Carninci, Marco Roncador, Shigeo Koyasu, Mary C. Farach-Carson, Shigehiro Yoshida, Swati Pradhan-Bhatt, Zuotian Tatum, Masanori Suzuki, Mette C. Jørgensen, Benoit Marchand, Misako Yoneda, James Prendergast, Noriko Ninomiya, Tom C. Freeman, Yulia A. Medvedeva, Niklas Mejhert, Jun Takai, Alexander D. Diehl, Akiko Saka, Marc van de Wetering, Takehiro Hashimoto, Naoto Kondo, Martin S. Taylor, Albert S.B. Edge, Mutsumi Kanamori-Katayama, Colin A. Semple, Alexander V. Favorov, Giuseppe Jurman, Toshiyuki Nakamura, Thomas J. Ha, Yuri Ishizu, Shannan J. Ho Sui, David A. Hume, Owen J. L. Rackham, Michela Fagiolini, Daisuke Sugiyama, Helena Persson, Hironori Satoh, Robert Young, Emily J. Wood, Akira Hasegawa, Yosuke Mizuno, Juha Kere, Hiroshi Tanaka, Michihira Tagami, A. Maxwell Burroughs, Sugata Roy, Sachi Kato, Taeko Dohi, Hai Fang, Chieko Kai, Fumio Nakahara, Christian Schmidl, Hiromi Nishiyori, Thierry Sengstag, Sven Guhl, Kei Iida, Antje Blumenthal, Boris Lenhard, Sarah Krampitz, Peter A C 't Hoen, Piotr J. Balwierz, Masayuki Yamamoto, Eri Saijyo, Suzana Savvi, Intikhab Alam Altschuler, Marina Lizio, Alison M. Meynert, Kazuyo Moro, Kenichi Nakazato, Sebastian Schmeier, Carlo Vittorio Cannistraci, Yasushi Okazaki, Yishai Shimoni, Kelly J Hitchens, Hideki Enomoto, Jeroen F. J. Laros, Naganari Ohkura, Ilya E. Vorontsov, Davide Albanese, Hiroshi Ohno, Yun Chen, Terrence F. Meehan, Mitsuhiro Ohshima, Mitsuko Hara, Emiliano Dalla, Roberto Verardo, Claudio Schneider, Takahiro Arakawa, Oliver Hofmann, Matthias Edinger, Mariko Okada-Hatakeyama, Susan E. Zabierowski, Shohei Noma, Yutaka Nakachi, Shoko Watanabe, Kaoru Kaida, Mitsuyoshi Murata, Takaaki Sugiyama, Hui Jia, Tetsuro Toyoda, Naoko Suzuki, Vsevolod J. Makeev, Naoko Takahashi Tagami, Hiroko Ohmiya, Christine L. Mummery, Emmanuel Dimont, Shiro Fukuda, Jun Kawai, Ivan V. Kulakovskiy, Anthony Mathelier, Nicolas Bertin, Hiroshi Kawamoto, Vanja Haberle, Robert Passier, Levon M. Khachigian, Yuki I. Kawamura, Jessica Severin, Valerio Orlando, Takeya Kasukawa, Teunis B. H. Geijtenbeek, Charles Plessy, Ernst J. Wolvetang, Stefano Gustincich, Shimon Sakaguchi, Erik van Nimwegen, Reto Guler, Martin C. Frith, Andrea Califano, Timo Lassmann, Peter Heutink, Boris R. Jankovic, Ri Ichiroh Manabe, Berit Lilje, Yari Ciani, Erik Arner, Rie Fujita, Robin Andersson, J Kenneth Baillie, Andrew T. Kwon, Atsutaka Kubosaki, Jun Ichi Furusawa, Soichi Kojima, Daniel Carbajo, Christine A. Wells, Tadasuke Nozaki, Rolf Swoboda, Hiroo Toyoda, Tony J. Kenna, Yoko Yamaguchi, Hideya Kawaji, Louise N. Winteringham, Cesare Furlanello, Michael Detmar, Judith S. Kempfle, Bogumil Kaczkowski, Gundula G. Schulze-Tanzil, Linda M. van den Berg, Alessandro Bonetti, Eivind Valen, Masayoshi Itoh, Yohei Yonekura, Guojun Sheng, Ulf Schaefer, Masahide Hamaguchi, Patrizia Rizzu, Anagha Joshi, Dmitry A. Ovchinnikov, Finn Drabløs, Christopher J. Mungall, Geoffrey J. Faulkner, Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, Human genetics, and NCA - Brain mechanisms in health and disease

Subjects
Transcription, Genetic, Cells, Messenger, Gene regulatory network, Mammalian promoter database, Biology, Article, Cell Line, Promoter Regions, Mice, Open Reading Frames, Essential, Atlases as Topic, Genetic, Animals, Cluster Analysis, Humans, Gene Regulatory Networks, RNA, Messenger, Promoter Regions, Genetic, Gene, Transcription factor, Cells, Cultured, Conserved Sequence, Genetics, Regulation of gene expression, Cultured, Multidisciplinary, Genes, Essential, Genome, Promoter, Molecular Sequence Annotation, Cap analysis gene expression, Genes, Gene Expression Regulation, Organ Specificity, Transcription Factors, Transcription Initiation Site, Transcriptome, RNA, Human genome, Transcription
Abstract

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

Published
2014
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