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Decreased replication origin activity in temporal transition regions
In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806585/ https://www.ncbi.nlm.nih.gov/pubmed/19951913 http://dx.doi.org/10.1083/jcb.200905144 |
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author | Guan, Zeqiang Hughes, Christina M. Kosiyatrakul, Settapong Norio, Paolo Sen, Ranjan Fiering, Steven Allis, C. David Bouhassira, Eric E. Schildkraut, Carl L. |
author_facet | Guan, Zeqiang Hughes, Christina M. Kosiyatrakul, Settapong Norio, Paolo Sen, Ranjan Fiering, Steven Allis, C. David Bouhassira, Eric E. Schildkraut, Carl L. |
author_sort | Guan, Zeqiang |
collection | PubMed |
description | In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, and enhancement of local histone modifications characteristic of active chromatin did not lead to origin activation. Moreover, very few replication initiation events were observed when two ectopic replication origin sequences were inserted into the TTR. These findings indicate that the Igh TTR represents a repressive compartment that inhibits replication initiation, thus maintaining the boundaries between early and late replication domains. |
format | Text |
id | pubmed-2806585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28065852010-05-30 Decreased replication origin activity in temporal transition regions Guan, Zeqiang Hughes, Christina M. Kosiyatrakul, Settapong Norio, Paolo Sen, Ranjan Fiering, Steven Allis, C. David Bouhassira, Eric E. Schildkraut, Carl L. J Cell Biol Research Articles In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, and enhancement of local histone modifications characteristic of active chromatin did not lead to origin activation. Moreover, very few replication initiation events were observed when two ectopic replication origin sequences were inserted into the TTR. These findings indicate that the Igh TTR represents a repressive compartment that inhibits replication initiation, thus maintaining the boundaries between early and late replication domains. The Rockefeller University Press 2009-11-30 /pmc/articles/PMC2806585/ /pubmed/19951913 http://dx.doi.org/10.1083/jcb.200905144 Text en © 2009 Guan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Guan, Zeqiang Hughes, Christina M. Kosiyatrakul, Settapong Norio, Paolo Sen, Ranjan Fiering, Steven Allis, C. David Bouhassira, Eric E. Schildkraut, Carl L. Decreased replication origin activity in temporal transition regions |
title | Decreased replication origin activity in temporal transition regions |
title_full | Decreased replication origin activity in temporal transition regions |
title_fullStr | Decreased replication origin activity in temporal transition regions |
title_full_unstemmed | Decreased replication origin activity in temporal transition regions |
title_short | Decreased replication origin activity in temporal transition regions |
title_sort | decreased replication origin activity in temporal transition regions |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806585/ https://www.ncbi.nlm.nih.gov/pubmed/19951913 http://dx.doi.org/10.1083/jcb.200905144 |
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