Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes.

Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Research Abstract Details 

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Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Abstract Text:

Alvaro Rada-Iglesias,Stefan Enroth,Adam Ameur,Christoph M Koch,Gayle K Clelland,Patricia Respuela-Alonso,Sarah Wilcox,Oliver M Dovey,Peter D Ellis,Cordelia F Langford,Ian Dunham,Jan Komorowski,Claes Wadelius,

Butyrate is a histone deacetylase inhibitor (HDACi) with anti-neoplastic properties, which theoretically reactivates epigenetically silenced genes by increasing global histone acetylation. However, recent studies indicate that a similar number or even more genes are down-regulated than up-regulated by this drug. We treated hepatocarcinoma HepG2 cells with butyrate and characterized the levels of acetylation at DNA-bound histones H3 and H4 by ChIP-chip along the ENCODE regions. In contrast to the global increases of histone acetylation, many genomic regions close to transcription start sites were deacetylated after butyrate exposure. In order to validate these findings, we found that both butyrate and trichostatin A treatment resulted in histone deacetylation at selected regions, while nucleosome loss or changes in histone H3 lysine 4 trimethylation (H3K4me3) did not occur in such locations. Furthermore, similar histone deacetylation events were observed when colon adenocarcinoma HT-29 cells were treated with butyrate. In addition, genes with deacetylated promoters were down-regulated by butyrate, and this was mediated at the transcriptional level by affecting RNA polymerase II (POLR2A) initiation/elongation. Finally, the global increase in acetylated histones was preferentially localized to the nuclear periphery, indicating that it might not be associated to euchromatin. Our results are significant for the evaluation of HDACi as anti-tumourogenic drugs, suggesting that previous models of action might need to be revised, and provides an explanation for the frequently observed repression of many genes during HDACi treatment.

Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Publishing Authors By Initials

A Rada-Iglesias,S Enroth,A Ameur,CM Koch,GK Clelland,P Respuela-Alonso,S Wilcox,OM Dovey,PD Ellis,CF Langford,I Dunham,J Komorowski,C Wadelius,

For similar genetic processes: gene expression regulation: protein modification, translational: protein processing, post-translational research abstracts see: genetic processes: gene expression regulation: protein modification, translational: protein processing, post-translational research

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Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Genome research

VOLUME: 17

Page Numbers: 708-19

Journal Abbreviation: Genome Res.

ISSN: 1088-9051

DAY: 3

MONTH: Jun

YEAR: 2007

Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9518021

Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Keywords Mesh Terms:

KEYWORDS: Protein Processing, Post-Translational

MESH TERMS: drug effects

Chemical & Substance for Abstract: Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes.

AFFILIATION: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, SE-751 05 Sweden. alvaro.rada@genpat.uu.se

Country: United States

AGENCY: United States NHGRI

GRANT: 5 U01 HG003168

ACRONYM: HG

MEDLINETA: Genome Res

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