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Histone deacetylase activity modulates alternative splicing
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SYSNO ASEP 0364989 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Histone deacetylase activity modulates alternative splicing Author(s) Hnilicová, Jarmila (UMG-J)
Hozeifi, Samira (UMG-J)
Dušková, Eva (UMG-J)
Icha, Jaroslav (UMG-J)
Tománková, Tereza (UMG-J)
Staněk, David (UMG-J) RIDSource Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 6, č. 2 (2011), e16727Number of pages 11 s. Language eng - English Country US - United States Keywords histone deacetylase ; alternative splicing ; chromatin Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP305/10/0424 GA ČR - Czech Science Foundation (CSF) KAN200520801 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000287036200036 DOI Annotation Increasing evidence suggests that splicing decisions are largely made when the nascent RNA is still associated with chromatin. Here we demonstrate that activity of histone deacetylases (HDACs) influences splice site selection. Using splicing-sensitive microarrays, we identified ca 700 genes whose splicing was altered after HDAC inhibition. We provided evidence that HDAC inhibition induced histone H4 acetylation and increased RNA Polymerase II (Pol II) processivity along an alternatively spliced element. In addition, HDAC inhibition reduced co-transcriptional association of the splicing regulator SRp40 with the target fibronectin exon. We further showed that the depletion of HDAC1 had similar effect on fibronectin alternative splicing as global HDAC inhibition. Importantly, this effect was reversed upon expression of mouse HDAC1 but not a catalytically inactive mutant. These results provide a molecular insight into a complex modulation of splicing by HDACs and chromatin modifications. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2012
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