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6 results on '"Gayle K. Clelland"'

1. Epigenetic Marking Prepares the Human HOXA Cluster for Activation During Differentiation of Pluripotent Cells

Author

Stuart P. Atkinson, Sarah Willcox, Rebecca Stewart, Ian Dunham, Joanna C. Fowler, Christoph M. Koch, Gayle K. Clelland, Majlinda Lako, and Lyle Armstrong

Subjects
Pluripotent Stem Cells, Cellular differentiation, Biology, Methylation, Cell Line, Epigenesis, Genetic, Histones, Histone H4, Mice, Carcinoma, Embryonal, Animals, Humans, Epigenetics, Hox gene, Induced pluripotent stem cell, Homeodomain Proteins, Genetics, Genome, Human, Lysine, Gene Expression Regulation, Developmental, Acetylation, Cell Differentiation, Cell Biology, Embryonic stem cell, Cell biology, Molecular Medicine, Developmental Biology, Bivalent chromatin, Human embryonic stem cell line
Abstract

Activation of Hox gene clusters is an early event in embryonic development since individual members play important roles in patterning of the body axis. Their functions require precise control of spatiotemporal expression to provide positional information for the cells of the developing embryo, and the manner by which this control is achieved has generated considerable interest. The situation is different in pluripotent cells, where HOX genes are not expressed but are held in potentio as bivalent chromatin domains, which are resolved upon differentiation to permit HOX cluster activation. In this study we have used differentiation of the pluripotent embryonal carcinoma cell line NTera2SP12 and the human embryonic stem cell line H9 to examine epigenetic changes that accompany activation of the HOXA cluster and show that specific genomic loci are marked by lysine methylation of histone H3 (H3K4 tri- and dimethyl, H3K9 trimethyl) and acetylation of histone H4 even in the undifferentiated cells. The precise locations of such modified histones may be involved in controlling the colinear expression of genes from the cluster. Disclosure of potential conflicts of interest is found at the end of this article.

Published
2008

2. Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes

Author

Patricia Respuela-Alonso, Sarah Wilcox, Alvaro Rada-Iglesias, Claes Wadelius, Stefan Enroth, Gayle K. Clelland, Adam Ameur, Peter D. Ellis, Ian Dunham, Oliver M. Dovey, Jan Komorowski, Christoph M. Koch, and Cordelia Langford

Subjects
medicine.drug_class, Adenocarcinoma, Biology, Histone Deacetylases, Article, Histones, Cell Line, Tumor, Histone methylation, Histone H2A, Genetics, medicine, Humans, Enzyme Inhibitors, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Histone deacetylase 5, Histone deacetylase 2, Gene Expression Profiling, Histone deacetylase inhibitor, Acetylation, HDAC4, Molecular biology, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, Butyrates, Histone methyltransferase, Colonic Neoplasms, H3K4me3, Protein Processing, Post-Translational
Abstract

Butyrate is a histone deacetylase inhibitor (HDACi) with anti-neoplastic properties, which theoretically reactivates epigenetically silenced genes by increasing global histone acetylation. However, recent studies indicate that a similar number or even more genes are down-regulated than up-regulated by this drug. We treated hepatocarcinoma HepG2 cells with butyrate and characterized the levels of acetylation at DNA-bound histones H3 and H4 by ChIP-chip along the ENCODE regions. In contrast to the global increases of histone acetylation, many genomic regions close to transcription start sites were deacetylated after butyrate exposure. In order to validate these findings, we found that both butyrate and trichostatin A treatment resulted in histone deacetylation at selected regions, while nucleosome loss or changes in histone H3 lysine 4 trimethylation (H3K4me3) did not occur in such locations. Furthermore, similar histone deacetylation events were observed when colon adenocarcinoma HT-29 cells were treated with butyrate. In addition, genes with deacetylated promoters were down-regulated by butyrate, and this was mediated at the transcriptional level by affecting RNA polymerase II (POLR2A) initiation/elongation. Finally, the global increase in acetylated histones was preferentially localized to the nuclear periphery, indicating that it might not be associated to euchromatin. Our results are significant for the evaluation of HDACi as anti-tumourogenic drugs, suggesting that previous models of action might need to be revised, and provides an explanation for the frequently observed repression of many genes during HDACi treatment.

Published
2007

3. The ENCODE (ENCyclopedia Of DNA Elements) Project

Author

Jonathan H. Dennis, Michael Brudno, Anindya Dutta, Richard M. Myers, Ian Dunham, Eduardo Eyras, S. S. Marticke, Alexandre Reymond, Anason S. Halees, Greg Schuler, M. G. Rosenfeld, Mikhail Nefedov, Robert E. Kingston, Elizabeth Anton, Tyra G. Wolfsberg, Alice C. Young, Kris A. Wetterstrand, C. K. Glass, Nancy F. Hansen, Gayle K. Clelland, Diane I. Schroeder, Jean L. Chang, H. Shin, Zhou Zhu, Nigel P. Carter, William Stafford Noble, Jenny McDowell, Ugrappa Nagalakshmi, Heike Fiegler, Philipp Kapranov, Peggy J. Farnham, Joanna C. Fowler, S. C. Harvey, Michael O. Dorschner, D. R. Inman, George V. Popescu, Jan-Jaap Wesselink, P. Groth, Baoli Zhu, H. Hirsch, James C. Wallace, Elise A. Feingold, S. Jin, Gabriel Robins, Thomas R. Gingeras, F. Denoeud, W. Tongprasit, Robert Castelo, Ross C. Hardison, John A. Stamatoyannopoulos, Joel Rozowsky, Eric A. Stone, Zheng Lian, J. E. Norton, Y. S. Kwon, Viktor Stolc, Michael C. Pirrung, Min-Feng Yu, A. Yang, W. J. Kent, Peter J. Sabo, Stephen Hartman, Stylianos E. Antonarakis, Tae Hoon Kim, H. Kim, Baishali Maskeri, Thomas Royce, R. Luna, Sherman M. Weissman, Tim Hubbard, Oliver M. Dovey, Ewan Birney, Kate R. Rosenbloom, Robert M. Andrews, Damian Keefe, Arend Sidow, D. Zhou, Jane Grimwood, Ulas Karaoz, Zhiping Weng, H. Burden, Michael C. Zody, Hiram Clawson, Gerry Bouffard, S. van Calcar, Mark Dickson, Kevin Struhl, Ingeborg Holt, Emmanouil T. Dermitzakis, T. J. Vasicek, Peter J. Good, Charles R. Cantor, Hari Tammana, Josée Dostie, Prachi Shah, Elliott H. Margulies, Peter D. Ellis, Mark S. Guyer, Christopher M. Taylor, Patrick A. Navas, Dione Kampa, Colin N. Dewey, Lior Pachter, Christof Koch, George Asimenos, James R R Whittle, Gregory E. Crawford, Jane B. Lian, Pamela J. Thomas, Kazutoyo Osoegawa, Webb Miller, Chunxu Qu, Nele Gheldof, Keith D. James, Sandeep Patel, Todd Richmond, Jacquelyn R. Idol, Michael A. Singer, Tomoko M. Tabuchi, Adam Siepel, Yutao Fu, David Vetrie, Long H. Nguyen, Michael Snyder, William H. Majoros, Michael R. Brent, Nathan D. Trinklein, Leah O. Barrera, Mark Gerstein, Srinka Ghosh, Sara J. Hartman, Jade P. Vinson, C. L. Middle, Sambath Chung, George Stamatoyannopoulos, Y. Nakayama, George M. Church, Job Dekker, Olof Emanuelsson, Julien Lagarde, Roderic Guigó, Marco A. Marra, Jeremy Schmutz, Daryl J. Thomas, Yong Yu, M. R. McCormick, Xiang-Dong Fu, Richard Humbert, Jennifer L. Ashurst, Alexander E. Urban, Sarah Wilcox, Ghia Euskirchen, Michael Kamal, Cordelia Langford, Jacquie Schein, Gregory M. Cooper, Paul Bertone, Eric S. Lander, C. Ding, Antonio Piccolboni, Steven L. Salzberg, Rhonda Harrison, Matthew J. Oberley, E. A. Sekinger, Mihaela Pertea, Bing Ren, H. K. Kim, Roland Green, Shelley Force Aldred, Laura Elnitski, Michael Hawrylycz, Andrew J. Mungall, Kerstin Lindblad-Toh, David B. Jaffe, Andreas D. Baxevanis, L. Liefer, Michele Clamp, David Haussler, Jill Cheng, John L. Rinn, S. Kamholz, Vicki L. Wraight, H. Sethi, Francis S. Collins, Steven J.M. Jones, Serafim Batzoglou, P. J. De Jong, Matthew E. Portnoy, Stefan Bekiranov, M. McArthur, Shu-Jin Luo, Eric D. Green, Robert W. Blakesley, Tarjei S. Mikkelsen, Z. Ye, Pawandeep Dhami, and Neerja Karnani

Subjects
Pilot phase, Pilot Projects, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, ENCODE, Access to Information, Evolution, Molecular, Annotation, chemistry.chemical_compound, Animals, Humans, International HapMap Project, Conserved Sequence, Publishing, Genetics, Internet, Multidisciplinary, Genome, Human, Information Dissemination, GENCODE, Computational Biology, Proteins, Genomics, Sequence Analysis, DNA, United States, National Institutes of Health (U.S.), chemistry, Encyclopedia, Human genome, Databases, Nucleic Acid, DNA
Abstract

The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

Published
2004

4. The landscape of histone modifications across 1% of the human genome in five human cell lines

Author

Nigel P. Carter, David Beare, Keith D. James, Phillippe Couttet, Christoph M. Koch, Sarah Wilcox, Ewan Birney, Gayle K. Clelland, Oliver M. Dovey, Joanna C. Fowler, Paul Flicek, Ulas Karaoz, Shane C. Dillon, David Vetrie, Peter D. Ellis, Gregory Lefebvre, Zhiping Weng, Alexander W. Bruce, Ian Dunham, Pawandeep Dhami, Cordelia Langford, and Robert Andrews

Subjects
Genetics, Transcription, Genetic, Genome, Human, Biology, Article, Histone H4, Histones, Histone H3, Histone H1, Histone methyltransferase, Histone H2A, Histone code, H3K4me3, Humans, K562 Cells, Protein Processing, Post-Translational, Genetics (clinical), Epigenomics, HeLa Cells
Abstract

We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including the ENCODE Consortium common cell lines GM06990 (lymphoblastoid) and HeLa-S3, as well as K562, HFL-1, and MOLT4, we identified clear patterns of histone modification profiles with respect to genomic features. H3K4me3, H3K4me2, and H3ac modifications are tightly associated with the transcriptional start sites (TSSs) of genes, while H3K4me1 and H4ac have more widespread distributions. TSSs reveal characteristic patterns of both types of modification present and the position relative to TSSs. These patterns differ between active and inactive genes and in particular the state of H3K4me3 and H3ac modifications is highly predictive of gene activity. Away from TSSs, modification sites are enriched in H3K4me1 and relatively depleted in H3K4me3 and H3ac. Comparison between cell lines identified differences in the histone modification profiles associated with transcriptional differences between the cell lines. These results provide an overview of the functional relationship among histone modifications and gene expression in human cells.

Published
2007

5. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Nan Jiang, Alfonso Valencia, Rachel A. Harte, Abigail Woodroffe, Michael Seringhaus, Andrew Haydock, Eugene Davydov, Todd M. Lowe, Peggy J. Farnham, Robert E. Thurman, Tyler Alioto, Adam Ameur, Morgan Park, Roderic Guigó, Archana Thakkapallayil, Philipp Kapranov, Francis S. Collins, Donna Karolchik, Stefan Washietl, Kerstin Lindblad-Toh, Michael L. Tress, Barbara E. Stranger, Gregory M. Cooper, Kun Wang, Thomas R. Gingeras, Serafim Batzoglou, Peter D. Ellis, Annie Yang, Stylianos E. Antonarakis, Jonghwan Kim, Robert M. Andrews, W. James Kent, Kuo Ping Chiu, Madhavan Ganesh, Jason D. Lieb, Shane Neph, Albin Sandelin, Michael Hawrylycz, Eric S. Lander, Matthew T. Weirauch, Nick Goldman, Alexander E. Urban, Ian Bell, Anason S. Halees, Jan Komorowski, Webb Miller, Kandhadayar G. Srinivasan, Evelyn Cheung, David B. Jaffe, Peter J. Good, Gregory Lefebvre, Yuko Yoshinaga, Sylvain Foissac, Alexander W. Bruce, Mark Dickson, Christoph M. Koch, Antigone S. Dimas, Zhengdong D. Zhang, Matthew J. Oberley, Paul I.W. de Bakker, Arend Sidow, Xueqing Zhang, Molly Weaver, Jane Rogers, Jacquelyn R. Idol, Jeff Goldy, Haiyan Huang, William Stafford Noble, Angie S. Hinrichs, Sandeep Patel, David A. Nix, Lluís Armengol, Siew Woh Choo, Hong Sain Ooi, Sara Van Calcar, Ivan Adzhubei, Job Dekker, Sara J. Cooper, Hari Tammana, Valerie Maduro, Jason A. Greenbaum, Bing Ren, Sharon L. Squazzo, Jennifer C. McDowell, Chikatoshi Kai, Ivo L. Hofacker, Ian Dunham, Peter J. Bickel, Nancy Holroyd, Eduardo Eyras, Julien Lagarde, Fei Yao, Man Yu, Piero Carninci, Chia-Lin Wei, Alice C. Young, Yong Yu, Daryl J. Thomas, George Asimenos, Xiaoqin Xu, Galt P. Barber, Andrea Tanzer, Juan I. Montoya-Burgos, Sujit Dike, Nathan Day, Gregory E. Crawford, Michele Clamp, Todd Richmond, Nuria Lopez-Bigas, Vishwanath R. Iyer, Ewan Birney, Richard Humbert, Gary C. Hon, David Swarbreck, Xiaobin Guan, Sarah Wilcox, Nate Heintzman, Josep F. Abril, Elaine R. Mardis, Stefan Enroth, Charlie W.H. Lee, Nicholas Matthews, Benedict Paten, Robert Castelo, Michael A. Singer, Mousheng Xu, Chiou Yu Choo, Nancy F. Hansen, Elizabeth Rosenzweig, Patrick A. Navas, Jacqueline Chrast, Brett E. Johnson, Jan O. Korbel, Simon Whelan, Stephen Hartman, Ulas Karaoz, Ingileif B. Hallgrímsdóttir, David Haussler, Michael R. Brent, Jill Cheng, Gonçalo R. Abecasis, Ann S. Zweig, Sherman M. Weissman, Michael O. Dorschner, Jin Lian, Vinsensius B. Vega, Cordelia Langford, Alexandre Reymond, Mark Gerstein, Pawandeep Dhami, Ola Wallerman, Huaiyang Jiang, Lior Pachter, James Taylor, Eric A. Stone, David R. Inman, Yijun Ruan, Peter E. Newburger, Roland Green, Ari Löytynoja, Shelley Force Aldred, Alvaro Rada-Iglesias, Baishali Maskeri, Joel Rozowsky, Jorg Drenkow, Colin N. Dewey, Srinka Ghosh, Yutao Fu, Kayla E. Smith, Xavier Estivill, Donna M. Muzny, Christine P. Bird, Tim Hubbard, Jana Hertel, Kristin Missal, Neerja Karnani, Ericka M. Johnson, Nan Zhang, Zhou Zhu, Stephen C. J. Parker, Minmei Hou, Charlotte N. Henrichsen, Heather A. Hirsch, Caroline Manzano, Laura A. Liefer, Kim C. Worley, Robert Baertsch, Mark S. Guyer, Ross C. Hardison, Zheng Lian, Hiram Clawson, Leah O. Barrera, Manja Lindemeyer, James Cuff, Chunxu Qu, Jun Kawai, Jennifer Hillman-Jackson, Eric D. Green, Robert W. Blakesley, Abel Ureta-Vidal, Rhona K. Stuart, Fabio Pardi, Peter J. Sabo, Edward A. Sekinger, John S. Mattick, Ankit Malhotra, Taane G. Clark, James G. R. Gilbert, James C. Mullikin, Deyou Zheng, Robert M. Kuhn, Tae Hoon Kim, M. Geoff Rosenfeld, Kirsten Lee, Jörg Hackermüller, Oliver M. Dovey, Deanna M. Church, Kyle J. Munn, Peter F. Stadler, Phillippe Couttet, Claudia Fried, Jaafar N. Haidar, Kris A. Wetterstrand, Wing-Kin Sung, Paul G. Giresi, Jia Qian Wu, Ruth Taylor, David A. Wheeler, Zarmik Moqtaderi, Adam Siepel, Michael Snyder, Ian Holmes, Jun Liu, Olof Emanuelsson, Kevin Struhl, Saurabh Asthana, Akshay Bhinge, Adam Frankish, Yoshihide Hayashizaki, Ghia Euskirchen, Joel D. Martin, Robert S. Fulton, Ugrappa Nagalakshmi, Heike Fiegler, Gayle K. Clelland, Shane C. Dillon, Fidencio Neri, Elliott H. Margulies, Sean Davis, Mark Bieda, Tristan Frum, Michael S. Kuehn, Heather Trumbower, Pamela J. Thomas, Kazutoyo Osoegawa, Richard A. Gibbs, Emmanouil T. Dermitzakis, Julian L. Huppert, Richard K. Wilson, Tina Graves, Zhiping Weng, Anthony Shafer, Baoli Zhu, Christopher K. Glass, Patrick J. Boyle, Hennady P. Shulha, Maxim Koriabine, Christoph Flamm, David Vetrie, Nigel P. Carter, Patrick Ng, Peter Kraus, John A. Stamatoyannopoulos, George M. Weinstock, Tim Massingham, Jane M. Lin, Damian Keefe, Jean L. Chang, Shamil R. Sunyaev, Sergey Nikolaev, Kate R. Rosenbloom, Carine Wyss, Hua Cao, Keith D. James, Michael C. Zody, Gerard G. Bouffard, Atif Shahab, Nathan D. Trinklein, James B. Brown, Erica Sodergren, Xiaodong Zhao, Rosa Luna, Sante Gnerre, Paul Flicek, Joanna C. Fowler, Andrew D. Kern, Jakob Skou Pedersen, David C. King, Anindya Dutta, Elise A. Feingold, Richard M. Myers, Richard Sandstrom, Catherine Ucla, Thomas D. Tullius, Mikhail Nefedov, Claes Wadelius, Jennifer Harrow, Christopher M. Taylor, Xiaoling Zhang, Pieter J. de Jong, Dermitzakis, Emmanouil, and Reymond, Alexandre

Subjects
DNA Replication, RNA, Messenger/genetics, Chromatin Immunoprecipitation, Heterozygote, RNA, Untranslated, Transcription, Genetic, Systems biology, Histones/metabolism, RNA, Untranslated/genetics, Pilot Projects, Genomics, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, ENCODE, Genome, Article, DNase-Seq, Histones, Evolution, Molecular, Exons/genetics, Humans, ddc:576.5, Transcription Factors/metabolism, RNA, Messenger, Conserved Sequence, Chromatin/genetics/metabolism, Genetics, Transcription, Genetic/ genetics, Multidisciplinary, Genome, Human, GENCODE, Genetic Variation, Exons, Chromatin, Genetic Variation/genetics, Regulatory Sequences, Nucleic Acid/ genetics, Human genome, Conserved Sequence/genetics, Transcription Initiation Site, Functional genomics, Genome, Human/ genetics, Transcription Factors, Protein Binding
Abstract

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view about chromatin structure has emerged, including its interrelationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded novel mechanistic and evolutionary insights about the functional landscape of the human genome. Together, these studies are defining a path forward to pursue a more-comprehensive characterisation of human genome function.

Published
2007

6. Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays

Author

Nigel P. Carter, Ian Dunham, Kenneth Wester, Pawandeep Dhami, Oliver M. Dovey, Stefan Enroth, David Vetrie, Adam Ameur, Ola Wallerman, Alvaro Rada-Iglesias, Christoph M. Koch, Gayle K. Clelland, Cordelia Langford, Robert Andrews, Fredrik Pontén, Keith D. James, Peter D. Ellis, Sarah Wilcox, Claes Wadelius, Vicki L. Wraight, and Jan Komorowski

Subjects
Chromatin Immunoprecipitation, Base pair, Response element, Computational biology, Biology, Histones, Metabolic Diseases, Cell Line, Tumor, Consensus Sequence, Genetics, Consensus sequence, Humans, Promoter Regions, Genetic, Molecular Biology, Transcription factor, Base Pairing, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Binding Sites, Genome, Human, General Medicine, Sequence Analysis, DNA, Chromatin, Hepatocyte Nuclear Factor 4, Hepatocyte Nuclear Factor 3-beta, Hepatocytes, Upstream Stimulatory Factors, Human genome, DNA microarray, Chromatin immunoprecipitation, Transcription Factors
Abstract

We present a detailed in vivo characterization of hepatocyte transcriptional regulation in HepG2 cells, using chromatin immunoprecipitation and detection on PCR fragment-based genomic tiling path arrays covering the encyclopedia of DNA element (ENCODE) regions. Our data suggest that HNF-4alpha and HNF-3beta, which were commonly bound to distal regulatory elements, may cooperate in the regulation of a large fraction of the liver transcriptome and that both HNF-4alpha and USF1 may promote H3 acetylation to many of their targets. Importantly, bioinformatic analysis of the sequences bound by each transcription factor (TF) shows an over-representation of motifs highly similar to the in vitro established consensus sequences. On the basis of these data, we have inferred tentative binding sites at base pair resolution. Some of these sites have been previously found by in vitro analysis and some were verified in vitro in this study. Our data suggests that a similar approach could be used for the in vivo characterization of all predicted/uncharacterized TF and that the analysis could be scaled to the whole genome.

Published
2005

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