| Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. | |
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MedLine Citation:
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PMID: 23152449 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant negative lamin A protein, known as progerin. Here we show that primary HGPS skin fibroblasts experience genome-wide correlated alterations in patterns of H3K27me3 deposition, DNA-lamin A/C associations, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains. We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells. Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin-lamina interactions. These changes may result in transcriptional misregulation and eventually trigger the global loss of spatial chromatin compartmentalization in late passage HGPS fibroblasts. |
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Authors:
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Rachel McCord; Ashley Nazario-Toole; Haoyue Zhang; Peter Chines; Ye Zhan; Michael Erdos; Francis Collins; Job Dekker; Kan Cao |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-14 |
Journal Detail:
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Title: Genome research Volume: - ISSN: 1549-5469 ISO Abbreviation: Genome Res. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9518021 Medline TA: Genome Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Massachusetts Medical School; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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