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Common fragile sites are characterized by histone hypoacetylation
Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusu...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773265/ https://www.ncbi.nlm.nih.gov/pubmed/19717471 http://dx.doi.org/10.1093/hmg/ddp410 |
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author | Jiang, Yanwen Lucas, Isabelle Young, David J. Davis, Elizabeth M. Karrison, Theodore Rest, Joshua S. Le Beau, Michelle M. |
author_facet | Jiang, Yanwen Lucas, Isabelle Young, David J. Davis, Elizabeth M. Karrison, Theodore Rest, Joshua S. Le Beau, Michelle M. |
author_sort | Jiang, Yanwen |
collection | PubMed |
description | Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusual sensitivity of CFSs to replication interference. To examine this hypothesis, we analyzed chromatin modification patterns within the six human CFSs with the highest levels of breakage, and their surrounding non-fragile regions (NCFSs). Chromatin at most of the CFSs analyzed has significantly less histone acetylation than that of their surrounding NCFSs. Trichostatin A and/or 5-azadeoxycytidine treatment reduced chromosome breakage at CFSs. Furthermore, chromatin at the most commonly expressed CFS, the FRA3B, is more resistant to micrococcal nuclease than that of the flanking non-fragile sequences. These results demonstrate that histone hypoacetylation is a characteristic epigenetic pattern of CFSs, and chromatin within CFSs might be relatively more compact than that of the NCFSs, indicating a role for chromatin conformation in genomic instability at CFSs. Moreover, lack of histone acetylation at CFSs may contribute to the defective response to replication stress characteristic of CFSs, leading to the genetic instability characteristic of this regions. |
format | Text |
id | pubmed-2773265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27732652009-11-05 Common fragile sites are characterized by histone hypoacetylation Jiang, Yanwen Lucas, Isabelle Young, David J. Davis, Elizabeth M. Karrison, Theodore Rest, Joshua S. Le Beau, Michelle M. Hum Mol Genet Articles Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusual sensitivity of CFSs to replication interference. To examine this hypothesis, we analyzed chromatin modification patterns within the six human CFSs with the highest levels of breakage, and their surrounding non-fragile regions (NCFSs). Chromatin at most of the CFSs analyzed has significantly less histone acetylation than that of their surrounding NCFSs. Trichostatin A and/or 5-azadeoxycytidine treatment reduced chromosome breakage at CFSs. Furthermore, chromatin at the most commonly expressed CFS, the FRA3B, is more resistant to micrococcal nuclease than that of the flanking non-fragile sequences. These results demonstrate that histone hypoacetylation is a characteristic epigenetic pattern of CFSs, and chromatin within CFSs might be relatively more compact than that of the NCFSs, indicating a role for chromatin conformation in genomic instability at CFSs. Moreover, lack of histone acetylation at CFSs may contribute to the defective response to replication stress characteristic of CFSs, leading to the genetic instability characteristic of this regions. Oxford University Press 2009-12-01 2009-08-28 /pmc/articles/PMC2773265/ /pubmed/19717471 http://dx.doi.org/10.1093/hmg/ddp410 Text en © The Author 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Jiang, Yanwen Lucas, Isabelle Young, David J. Davis, Elizabeth M. Karrison, Theodore Rest, Joshua S. Le Beau, Michelle M. Common fragile sites are characterized by histone hypoacetylation |
title | Common fragile sites are characterized by histone hypoacetylation |
title_full | Common fragile sites are characterized by histone hypoacetylation |
title_fullStr | Common fragile sites are characterized by histone hypoacetylation |
title_full_unstemmed | Common fragile sites are characterized by histone hypoacetylation |
title_short | Common fragile sites are characterized by histone hypoacetylation |
title_sort | common fragile sites are characterized by histone hypoacetylation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773265/ https://www.ncbi.nlm.nih.gov/pubmed/19717471 http://dx.doi.org/10.1093/hmg/ddp410 |
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