Histone deacetylase activity modulates alternative splicing

0364989 - ÚMG 2012 RIV US eng J - Článek v odborném periodiku
Hnilicová, Jarmila - Hozeifi, Samira - Dušková, Eva - Icha, Jaroslav - Tománková, Tereza - Staněk, David
Histone deacetylase activity modulates alternative splicing.
PLoS ONE. Roč. 6, č. 2 (2011), e16727. ISSN 1932-6203. E-ISSN 1932-6203
Grant CEP: GA ČR GAP305/10/0424; GA AV ČR KAN200520801
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: histone deacetylase * alternative splicing * chromatin
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.092, rok: 2011

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.
Trvalý link: http://hdl.handle.net/11104/0200338