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Human Genome Replication Proceeds through Four Chromatin States
Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and diffe...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794905/ https://www.ncbi.nlm.nih.gov/pubmed/24130466 http://dx.doi.org/10.1371/journal.pcbi.1003233 |
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author | Julienne, Hanna Zoufir, Azedine Audit, Benjamin Arneodo, Alain |
author_facet | Julienne, Hanna Zoufir, Azedine Audit, Benjamin Arneodo, Alain |
author_sort | Julienne, Hanna |
collection | PubMed |
description | Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and differentiation or in response to the environment. Paradoxically, the molecular mechanisms that regulate the initiation and the maintenance of the spatio-temporal replication program in higher eukaryotes, and in particular their links to epigenetic modifications, still remain elusive. By integrative analysis of the genome-wide distributions of thirteen epigenetic marks in the human cell line K562, at the 100 kb resolution of corresponding mean replication timing (MRT) data, we identify four major groups of chromatin marks with shared features. These states have different MRT, namely from early to late replicating, replication proceeds though a transcriptionally active euchromatin state (C1), a repressive type of chromatin (C2) associated with polycomb complexes, a silent state (C3) not enriched in any available marks, and a gene poor HP1-associated heterochromatin state (C4). When mapping these chromatin states inside the megabase-sized U-domains (U-shaped MRT profile) covering about 50% of the human genome, we reveal that the associated replication fork polarity gradient corresponds to a directional path across the four chromatin states, from C1 at U-domains borders followed by C2, C3 and C4 at centers. Analysis of the other genome half is consistent with early and late replication loci occurring in separate compartments, the former correspond to gene-rich, high-GC domains of intermingled chromatin states C1 and C2, whereas the latter correspond to gene-poor, low-GC domains of alternating chromatin states C3 and C4 or long C4 domains. This new segmentation sheds a new light on the epigenetic regulation of the spatio-temporal replication program in human and provides a framework for further studies in different cell types, in both health and disease. |
format | Online Article Text |
id | pubmed-3794905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37949052013-10-15 Human Genome Replication Proceeds through Four Chromatin States Julienne, Hanna Zoufir, Azedine Audit, Benjamin Arneodo, Alain PLoS Comput Biol Research Article Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and differentiation or in response to the environment. Paradoxically, the molecular mechanisms that regulate the initiation and the maintenance of the spatio-temporal replication program in higher eukaryotes, and in particular their links to epigenetic modifications, still remain elusive. By integrative analysis of the genome-wide distributions of thirteen epigenetic marks in the human cell line K562, at the 100 kb resolution of corresponding mean replication timing (MRT) data, we identify four major groups of chromatin marks with shared features. These states have different MRT, namely from early to late replicating, replication proceeds though a transcriptionally active euchromatin state (C1), a repressive type of chromatin (C2) associated with polycomb complexes, a silent state (C3) not enriched in any available marks, and a gene poor HP1-associated heterochromatin state (C4). When mapping these chromatin states inside the megabase-sized U-domains (U-shaped MRT profile) covering about 50% of the human genome, we reveal that the associated replication fork polarity gradient corresponds to a directional path across the four chromatin states, from C1 at U-domains borders followed by C2, C3 and C4 at centers. Analysis of the other genome half is consistent with early and late replication loci occurring in separate compartments, the former correspond to gene-rich, high-GC domains of intermingled chromatin states C1 and C2, whereas the latter correspond to gene-poor, low-GC domains of alternating chromatin states C3 and C4 or long C4 domains. This new segmentation sheds a new light on the epigenetic regulation of the spatio-temporal replication program in human and provides a framework for further studies in different cell types, in both health and disease. Public Library of Science 2013-10-10 /pmc/articles/PMC3794905/ /pubmed/24130466 http://dx.doi.org/10.1371/journal.pcbi.1003233 Text en © 2013 Julienne 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 Julienne, Hanna Zoufir, Azedine Audit, Benjamin Arneodo, Alain Human Genome Replication Proceeds through Four Chromatin States |
title | Human Genome Replication Proceeds through Four Chromatin States |
title_full | Human Genome Replication Proceeds through Four Chromatin States |
title_fullStr | Human Genome Replication Proceeds through Four Chromatin States |
title_full_unstemmed | Human Genome Replication Proceeds through Four Chromatin States |
title_short | Human Genome Replication Proceeds through Four Chromatin States |
title_sort | human genome replication proceeds through four chromatin states |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794905/ https://www.ncbi.nlm.nih.gov/pubmed/24130466 http://dx.doi.org/10.1371/journal.pcbi.1003233 |
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