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Distinct epigenetic features of differentiation-regulated replication origins
BACKGROUND: Eukaryotic genome duplication starts at discrete sequences (replication origins) that coordinate cell cycle progression, ensure genomic stability and modulate gene expression. Origins share some sequence features, but their activity also responds to changes in transcription and cellular...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862150/ https://www.ncbi.nlm.nih.gov/pubmed/27168766 http://dx.doi.org/10.1186/s13072-016-0067-3 |
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author | Smith, Owen K. Kim, RyanGuk Fu, Haiqing Martin, Melvenia M. Lin, Chii Mei Utani, Koichi Zhang, Ya Marks, Anna B. Lalande, Marc Chamberlain, Stormy Libbrecht, Maxwell W. Bouhassira, Eric E. Ryan, Michael C. Noble, William S. Aladjem, Mirit I. |
author_facet | Smith, Owen K. Kim, RyanGuk Fu, Haiqing Martin, Melvenia M. Lin, Chii Mei Utani, Koichi Zhang, Ya Marks, Anna B. Lalande, Marc Chamberlain, Stormy Libbrecht, Maxwell W. Bouhassira, Eric E. Ryan, Michael C. Noble, William S. Aladjem, Mirit I. |
author_sort | Smith, Owen K. |
collection | PubMed |
description | BACKGROUND: Eukaryotic genome duplication starts at discrete sequences (replication origins) that coordinate cell cycle progression, ensure genomic stability and modulate gene expression. Origins share some sequence features, but their activity also responds to changes in transcription and cellular differentiation status. RESULTS: To identify chromatin states and histone modifications that locally mark replication origins, we profiled origin distributions in eight human cell lines representing embryonic and differentiated cell types. Consistent with a role of chromatin structure in determining origin activity, we found that cancer and non-cancer cells of similar lineages exhibited highly similar replication origin distributions. Surprisingly, our study revealed that DNase hypersensitivity, which often correlates with early replication at large-scale chromatin domains, did not emerge as a strong local determinant of origin activity. Instead, we found that two distinct sets of chromatin modifications exhibited strong local associations with two discrete groups of replication origins. The first origin group consisted of about 40,000 regions that actively initiated replication in all cell types and preferentially colocalized with unmethylated CpGs and with the euchromatin markers, H3K4me3 and H3K9Ac. The second group included origins that were consistently active in cells of a single type or lineage and preferentially colocalized with the heterochromatin marker, H3K9me3. Shared origins replicated throughout the S-phase of the cell cycle, whereas cell-type-specific origins preferentially replicated during late S-phase. CONCLUSIONS: These observations are in line with the hypothesis that differentiation-associated changes in chromatin and gene expression affect the activation of specific replication origins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0067-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4862150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48621502016-05-11 Distinct epigenetic features of differentiation-regulated replication origins Smith, Owen K. Kim, RyanGuk Fu, Haiqing Martin, Melvenia M. Lin, Chii Mei Utani, Koichi Zhang, Ya Marks, Anna B. Lalande, Marc Chamberlain, Stormy Libbrecht, Maxwell W. Bouhassira, Eric E. Ryan, Michael C. Noble, William S. Aladjem, Mirit I. Epigenetics Chromatin Research BACKGROUND: Eukaryotic genome duplication starts at discrete sequences (replication origins) that coordinate cell cycle progression, ensure genomic stability and modulate gene expression. Origins share some sequence features, but their activity also responds to changes in transcription and cellular differentiation status. RESULTS: To identify chromatin states and histone modifications that locally mark replication origins, we profiled origin distributions in eight human cell lines representing embryonic and differentiated cell types. Consistent with a role of chromatin structure in determining origin activity, we found that cancer and non-cancer cells of similar lineages exhibited highly similar replication origin distributions. Surprisingly, our study revealed that DNase hypersensitivity, which often correlates with early replication at large-scale chromatin domains, did not emerge as a strong local determinant of origin activity. Instead, we found that two distinct sets of chromatin modifications exhibited strong local associations with two discrete groups of replication origins. The first origin group consisted of about 40,000 regions that actively initiated replication in all cell types and preferentially colocalized with unmethylated CpGs and with the euchromatin markers, H3K4me3 and H3K9Ac. The second group included origins that were consistently active in cells of a single type or lineage and preferentially colocalized with the heterochromatin marker, H3K9me3. Shared origins replicated throughout the S-phase of the cell cycle, whereas cell-type-specific origins preferentially replicated during late S-phase. CONCLUSIONS: These observations are in line with the hypothesis that differentiation-associated changes in chromatin and gene expression affect the activation of specific replication origins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0067-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-10 /pmc/articles/PMC4862150/ /pubmed/27168766 http://dx.doi.org/10.1186/s13072-016-0067-3 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Smith, Owen K. Kim, RyanGuk Fu, Haiqing Martin, Melvenia M. Lin, Chii Mei Utani, Koichi Zhang, Ya Marks, Anna B. Lalande, Marc Chamberlain, Stormy Libbrecht, Maxwell W. Bouhassira, Eric E. Ryan, Michael C. Noble, William S. Aladjem, Mirit I. Distinct epigenetic features of differentiation-regulated replication origins |
title | Distinct epigenetic features of differentiation-regulated replication origins |
title_full | Distinct epigenetic features of differentiation-regulated replication origins |
title_fullStr | Distinct epigenetic features of differentiation-regulated replication origins |
title_full_unstemmed | Distinct epigenetic features of differentiation-regulated replication origins |
title_short | Distinct epigenetic features of differentiation-regulated replication origins |
title_sort | distinct epigenetic features of differentiation-regulated replication origins |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862150/ https://www.ncbi.nlm.nih.gov/pubmed/27168766 http://dx.doi.org/10.1186/s13072-016-0067-3 |
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