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Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human

Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We an...

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Autores principales: Pu, Shuye, Turinsky, Andrei L., Vlasblom, James, On, Tuan, Xiong, Xuejian, Emili, Andrew, Zhang, Zhaolei, Greenblatt, Jack, Parkinson, John, Wodak, Shoshana J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993927/
https://www.ncbi.nlm.nih.gov/pubmed/21124763
http://dx.doi.org/10.1371/journal.pone.0014122
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author Pu, Shuye
Turinsky, Andrei L.
Vlasblom, James
On, Tuan
Xiong, Xuejian
Emili, Andrew
Zhang, Zhaolei
Greenblatt, Jack
Parkinson, John
Wodak, Shoshana J.
author_facet Pu, Shuye
Turinsky, Andrei L.
Vlasblom, James
On, Tuan
Xiong, Xuejian
Emili, Andrew
Zhang, Zhaolei
Greenblatt, Jack
Parkinson, John
Wodak, Shoshana J.
author_sort Pu, Shuye
collection PubMed
description Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins) in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.
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spelling pubmed-29939272010-12-01 Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human Pu, Shuye Turinsky, Andrei L. Vlasblom, James On, Tuan Xiong, Xuejian Emili, Andrew Zhang, Zhaolei Greenblatt, Jack Parkinson, John Wodak, Shoshana J. PLoS One Research Article Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins) in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available. Public Library of Science 2010-11-29 /pmc/articles/PMC2993927/ /pubmed/21124763 http://dx.doi.org/10.1371/journal.pone.0014122 Text en Pu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pu, Shuye
Turinsky, Andrei L.
Vlasblom, James
On, Tuan
Xiong, Xuejian
Emili, Andrew
Zhang, Zhaolei
Greenblatt, Jack
Parkinson, John
Wodak, Shoshana J.
Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title_full Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title_fullStr Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title_full_unstemmed Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title_short Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human
title_sort expanding the landscape of chromatin modification (cm)-related functional domains and genes in human
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993927/
https://www.ncbi.nlm.nih.gov/pubmed/21124763
http://dx.doi.org/10.1371/journal.pone.0014122
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