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Histone deacetylase activity modulates alternative splicing
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SYSNO ASEP 0364989 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Histone deacetylase activity modulates alternative splicing Tvůrce(i) Hnilicová, Jarmila (UMG-J)
Hozeifi, Samira (UMG-J)
Dušková, Eva (UMG-J)
Icha, Jaroslav (UMG-J)
Tománková, Tereza (UMG-J)
Staněk, David (UMG-J) RIDZdroj.dok. PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 6, č. 2 (2011), e16727Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova histone deacetylase ; alternative splicing ; chromatin Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP305/10/0424 GA ČR - Grantová agentura ČR KAN200520801 GA AV ČR - Akademie věd CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000287036200036 DOI 10.1371/journal.pone.0016727 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2012
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