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Article: Altered promoter nucleosome positioning is an early event in gene silencing

TitleAltered promoter nucleosome positioning is an early event in gene silencing
Authors
KeywordsCancer
Hypermethylation
Gene silencing
DNA methylation
Nucleosome
Issue Date2014
Citation
Epigenetics, 2014, v. 9, n. 10, p. 1422-1430 How to Cite?
Abstract© 2014 Taylor & Francis Group, LLC. Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1 and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1 silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.
Persistent Identifierhttp://hdl.handle.net/10722/251087
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 1.149
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHesson, Luke B.-
dc.contributor.authorSloane, Mathew A.-
dc.contributor.authorWong, Jason W.H.-
dc.contributor.authorNunez, Andrea C.-
dc.contributor.authorSrivastava, Sameer-
dc.contributor.authorNg, Benedict-
dc.contributor.authorHawkins, Nicholas J.-
dc.contributor.authorBourke, Michael J.-
dc.contributor.authorWard, Robyn L.-
dc.date.accessioned2018-02-01T01:54:32Z-
dc.date.available2018-02-01T01:54:32Z-
dc.date.issued2014-
dc.identifier.citationEpigenetics, 2014, v. 9, n. 10, p. 1422-1430-
dc.identifier.issn1559-2294-
dc.identifier.urihttp://hdl.handle.net/10722/251087-
dc.description.abstract© 2014 Taylor & Francis Group, LLC. Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1 and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1 silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.-
dc.languageeng-
dc.relation.ispartofEpigenetics-
dc.subjectCancer-
dc.subjectHypermethylation-
dc.subjectGene silencing-
dc.subjectDNA methylation-
dc.subjectNucleosome-
dc.titleAltered promoter nucleosome positioning is an early event in gene silencing-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.4161/15592294.2014.970077-
dc.identifier.pmid25437056-
dc.identifier.scopuseid_2-s2.0-84922008831-
dc.identifier.volume9-
dc.identifier.issue10-
dc.identifier.spage1422-
dc.identifier.epage1430-
dc.identifier.eissn1559-2308-
dc.identifier.isiWOS:000348378900012-
dc.identifier.issnl1559-2294-

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