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Your search keyword '"Ozadam, Hakan"' showing total 37 results
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37 results on '"Ozadam, Hakan"'

1. Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling.

Author

Kejiou, Nevraj S, Ilan, Lena, Aigner, Stefan, Luo, Enching, Tonn, Tori, Ozadam, Hakan, Lee, Muyoung, Cole, Gregory B, Rabano, Ines, Rajakulendran, Nishani, Yee, Brian A, Najafabadi, Hamed S, Moraes, Trevor F, Angers, Stephane, Yeo, Gene W, Cenik, Can, and Palazzo, Alexander F

Subjects
Ribosomes, Humans, Pyruvate Kinase, Glutamates, Lysine, Proteomics, Protein Biosynthesis, Poly ADP Ribosylation, Genetics, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology
Abstract

In light of the numerous studies identifying post-transcriptional regulators on the surface of the endoplasmic reticulum (ER), we asked whether there are factors that regulate compartment specific mRNA translation in human cells. Using a proteomic survey of spatially regulated polysome interacting proteins, we identified the glycolytic enzyme Pyruvate Kinase M (PKM) as a cytosolic (i.e. ER-excluded) polysome interactor and investigated how it influences mRNA translation. We discovered that the PKM-polysome interaction is directly regulated by ADP levels-providing a link between carbohydrate metabolism and mRNA translation. By performing enhanced crosslinking immunoprecipitation-sequencing (eCLIP-seq), we found that PKM crosslinks to mRNA sequences that are immediately downstream of regions that encode lysine- and glutamate-enriched tracts. Using ribosome footprint protection sequencing, we found that PKM binding to ribosomes causes translational stalling near lysine and glutamate encoding sequences. Lastly, we observed that PKM recruitment to polysomes is dependent on poly-ADP ribosylation activity (PARylation)-and may depend on co-translational PARylation of lysine and glutamate residues of nascent polypeptide chains. Overall, our study uncovers a novel role for PKM in post-transcriptional gene regulation, linking cellular metabolism and mRNA translation.

Published
2023

3. RiboGraph: an interactive visualization system for ribosome profiling data at read length resolution.

Author

Chacko, Jonathan, Ozadam, Hakan, and Cenik, Can

Subjects
*SOURCE code, *RESEARCH personnel, *GENETIC translation, *DATA visualization, *RIBOSOMES, *DATA analysis
Abstract

Motivation Ribosome profiling is a widely-used technique for measuring ribosome occupancy at nucleotide resolution. However, the need to analyze this data at nucleotide resolution introduces unique challenges in data visualization and analyses. Results In this study, we introduce RiboGraph, a dedicated visualization tool designed to work with.ribo files, a specialized and efficient format for ribosome occupancy data. Unlike existing solutions that rely on large alignment files and time-consuming preprocessing steps, RiboGraph operates on a purpose designed compact file type. This efficiency allows for interactive, real-time visualization at ribosome-protected fragment length resolution. By providing an integrated toolset, RiboGraph empowers researchers to conduct comprehensive visual analysis of ribosome occupancy data. Availability and implementation Source code, step-by-step installation instructions and links to documentation are available on GitHub: https://github.com/ribosomeprofiling/ribograph. On the same page, we provide test files and a step-by-step tutorial highlighting the key features of RiboGraph. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Integrative detection and analysis of structural variation in cancer genomes

Author

Dixon, Jesse R., Xu, Jie, Dileep, Vishnu, Zhan, Ye, Song, Fan, Le, Victoria T., Yardımcı, Galip Gürkan, Chakraborty, Abhijit, Bann, Darrin V., Wang, Yanli, Clark, Royden, Zhang, Lijun, Yang, Hongbo, Liu, Tingting, Iyyanki, Sriranga, An, Lin, Pool, Christopher, Sasaki, Takayo, Rivera-Mulia, Juan Carlos, Ozadam, Hakan, Lajoie, Bryan R., Kaul, Rajinder, Buckley, Michael, Lee, Kristen, Diegel, Morgan, Pezic, Dubravka, Ernst, Christina, Hadjur, Suzana, Odom, Duncan T., Stamatoyannopoulos, John A., Broach, James R., Hardison, Ross C., Ay, Ferhat, Noble, William Stafford, Dekker, Job, Gilbert, David M., and Yue, Feng

Published
2018
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10. Measuring the reproducibility and quality of Hi-C data

Author

Yardımcı, Galip Gürkan, Ozadam, Hakan, Sauria, Michael E. G., Ursu, Oana, Yan, Koon-Kiu, Yang, Tao, Chakraborty, Abhijit, Kaul, Arya, Lajoie, Bryan R., Song, Fan, Zhan, Ye, Ay, Ferhat, Gerstein, Mark, Kundaje, Anshul, Li, Qunhua, Taylor, James, Yue, Feng, Dekker, Job, and Noble, William S.

Published
2019
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13. Systematic evaluation of chromosome conformation capture assays

Author

Oksuz, Betul Akgol, primary, Yang, Liyan, additional, Abraham, Sameer, additional, Venev, Sergey V., additional, Krietenstein, Nils, additional, Parsi, Krishna Mohan, additional, Ozadam, Hakan, additional, Oomen, Marlies E., additional, Nand, Ankita, additional, Mao, Hui, additional, Genga, Ryan MJ, additional, Maehr, Rene, additional, Rando, Oliver J., additional, Mirny, Leonid A., additional, Gibcus, Johan Harmen, additional, and Dekker, Job, additional

Published
2020
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22. Additional file 1: of Measuring the reproducibility and quality of Hi-C data

Author

YardÄąmcÄą, Galip, Ozadam, Hakan, Sauria, Michael, Ursu, Oana, Koon-Kiu Yan, Yang, Tao, Abhijit Chakraborty, Arya Kaul, Lajoie, Bryan, Song, Fan, Zhan, Ye, Ay, Ferhat, Gerstein, Mark, Anshul Kundaje, Qunhua Li, Taylor, James, Yue, Feng, Dekker, Job, and Noble, William

Abstract

Supplementary figures and tables describing additional results and the datasets used in this study, respectively. (DOCX 5 kb)

Published
2019
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23. The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome

Author

Gdula, Michal R, Nesterova, Tatyana B, Pintacuda, Greta, Godwin, Jonathan, Zhan, Ye, Ozadam, Hakan, McClellan, Michael, Moralli, Daniella, Krueger, Felix, Green, Catherine M, Reik, Wolf, Kriaucionis, Skirmantas, Heard, Edith, Dekker, Job, Brockdorff, Neil, University of Oxford [Oxford], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), The Wellcome Trust Centre for Human Genetics [Oxford], The Babraham Institute [Cambridge, UK], Institut Curie [Paris], Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chaire Epigénétique et mémoire cellulaire, Collège de France (CdF (institution)), Gdula, Michal R [0000-0002-8667-7359], Nesterova, Tatyana B [0000-0001-7740-4386], Pintacuda, Greta [0000-0001-5126-2279], Zhan, Ye [0000-0001-9280-1718], Moralli, Daniella [0000-0001-7977-8496], Krueger, Felix [0000-0002-5513-3324], Heard, Edith [0000-0001-8052-7117], Dekker, Job [0000-0001-5631-0698], and Apollo - University of Cambridge Repository

Subjects
Male, Transcriptional Activation, Chromosomal Proteins, Non-Histone, Science, [SDV]Life Sciences [q-bio], Polycomb-Group Proteins, Exons, DNA Methylation, Fibroblasts, Article, Cell Line, Histones, Gene Knockout Techniques, Mice, X Chromosome Inactivation, Animals, Point Mutation, CpG Islands, Female, lcsh:Q, CRISPR-Cas Systems, lcsh:Science, Alleles
Abstract

The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation of two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 mutant cells reveals the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including A/B compartments and partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred following SmcHD1 knockout in a somatic cell model, but in this case, independent of Xi gene derepression. We conclude that SmcHD1 is a key factor in defining the unique chromosome architecture of Xi., The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.

Published
2018

26. The non-canonical SMC protein SmcHD1 antagonises TAD formation on the inactive X chromosome

Author

Gdula, Michal R, primary, Nesterova, Tatyana B, additional, Pintacuda, Greta, additional, Godwin, Jonathan, additional, Zhan, Ye, additional, Ozadam, Hakan, additional, McClellan, Michael, additional, Moralli, Daniella, additional, Krueger, Felix, additional, Green, Catherine M, additional, Reik, Wolf, additional, Kriaucionis, Skirmantas, additional, Heard, Edith, additional, Dekker, Job, additional, and Brockdorff, Neil, additional

Published
2018
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30. Measuring the reproducibility and quality of Hi-C data

Author

Yardımcı, Galip Gürkan, primary, Ozadam, Hakan, additional, Sauria, Michael E.G., additional, Ursu, Oana, additional, Yan, Koon-Kiu, additional, Yang, Tao, additional, Chakraborty, Abhijit, additional, Kaul, Arya, additional, Lajoie, Bryan R., additional, Song, Fan, additional, Zhang, Ye, additional, Ay, Ferhat, additional, Gerstein, Mark, additional, Kundaje, Anshul, additional, Li, Qunhua, additional, Taylor, James, additional, Yue, Feng, additional, Dekker, Job, additional, and Noble, William S., additional

Published
2017
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31. An Integrative Framework for Detecting Structural Variations in Cancer Genomes

Author

Dixon, Jesse R., primary, Xu, Jie, additional, Dileep, Vishnu, additional, Zhan, Ye, additional, Song, Fan, additional, Le, Victoria T., additional, Yardimci, Galip Gürkan, additional, Chakraborty, Abhijit, additional, Bann, Darrin V., additional, Wang, Yanli, additional, Clark, Royden, additional, Zhang, Lijun, additional, Yang, Hongbo, additional, Liu, Tingting, additional, Iyyanki, Sriranga, additional, An, Lin, additional, Pool, Christopher, additional, Sasaki, Takayo, additional, Rivera Mulia, Juan Carlos, additional, Ozadam, Hakan, additional, Lajoie, Bryan R., additional, Kaul, Rajinder, additional, Buckley, Michael, additional, Lee, Kristen, additional, Diegel, Morgan, additional, Pezic, Dubravka, additional, Ernst, Christina, additional, Hadjur, Suzana, additional, Odom, Duncan T., additional, Stamatoyannopoulos, John A., additional, Broach, James R., additional, Hardison, Ross, additional, Ay, Ferhat, additional, Noble, William Stafford, additional, Dekker, Job, additional, Gilbert, David M., additional, and Yue, Feng, additional

Published
2017
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35. Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes.

Author

Liu Y, Hoskins I, Geng M, Zhao Q, Chacko J, Qi K, Persyn L, Wang J, Zheng D, Zhong Y, Rao S, Park D, Cenik ES, Agarwal V, Ozadam H, and Cenik C

Abstract

Characterization of shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and novel biological functions. However, it is unclear if such coordination extends to translation, a critical step in gene expression. Here, we uniformly analyzed 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept of Translation Efficiency Covariation (TEC), identifying coordinated translation patterns across cell types. We nominate potential mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and helps uncover gene functions. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish translational covariation as a conserved organizing principle of mammalian transcriptomes., Competing Interests: DECLARATION OF INTERESTS D.Z., J.W. and V.A. are employees of Sanofi and may hold shares and/or stock options in the company. H.O. is an employee of Sail Biomedicines.

Published
2024
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36. The Ribosome Assembly Factor Reh1 is Released from the Polypeptide Exit Tunnel in the Pioneer Round of Translation.

Author

Musalgaonkar S, Yelland J, Chitale R, Rao S, Ozadam H, Cenik C, Taylor D, and Johnson A

Abstract

Assembly of functional ribosomal subunits and successfully delivering them to the translating pool is a prerequisite for protein synthesis and cell growth. In S. cerevisiae, the ribosome assembly factor Reh1 binds to pre-60S subunits at a late stage during their cytoplasmic maturation. Previous work shows that the C-terminus of Reh1 inserts into the polypeptide exit tunnel (PET) of the pre-60S subunit. Unlike canonical assembly factors, which associate exclusively with pre-60S subunits, we observed that Reh1 sediments with polysomes in addition to free 60S subunits. We therefore investigated the intriguing possibility that Reh1 remains associated with 60S subunits after the release of the anti-association factor Tif6 and after subunit joining. Here, we show that Reh1-bound nascent 60S subunits associate with 40S subunits to form actively translating ribosomes. Using selective ribosome profiling, we found that Reh1-bound ribosomes populate open reading frames near start codons. Reh1-bound ribosomes are also strongly enriched for initiator tRNA, indicating they are associated with early elongation events. Using single particle cryo-electron microscopy to image cycloheximide-arrested Reh1-bound 80S ribosomes, we found that Reh1-bound 80S contain A site peptidyl tRNA, P site tRNA and eIF5A indicating that Reh1 does not dissociate from 60S until early stages of translation elongation. We propose that Reh1 is displaced by the elongating peptide chain. These results identify Reh1 as the last assembly factor released from the nascent 60S subunit during its pioneer round of translation.

Published
2023
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37. Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein.

Author

Rao S, Hoskins I, Tonn T, Garcia PD, Ozadam H, Cenik ES, and Cenik C

Abstract

Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, Nsp1, for shutting down host translation. However, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing Nsp1. We perform RNA-Seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation level. We discover a functionally-coherent subset of human genes are preferentially translated in the context of Nsp1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we uncovered a remarkable enrichment of 5' terminal oligo-pyrimidine (TOP) tracts among preferentially translated genes. Using reporter assays, we validated that 5' UTRs from TOP transcripts can drive preferential expression in the presence of NSP1. Finally, we found that LARP1, a key effector protein in the mTOR pathway may contribute to preferential translation of TOP transcripts in response to Nsp1 expression. Collectively, our study suggests fine tuning of host gene expression and translation by Nsp1 despite its global repressive effect on host protein synthesis.

Published
2021
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