There is increasing evidence to suggest 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 ∼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.
- MeSH
- alternativní sestřih účinky léků genetika fyziologie MeSH
- HeLa buňky MeSH
- histondeacetylasa 1 genetika fyziologie MeSH
- histondeacetylasy genetika metabolismus fyziologie MeSH
- inhibitory histondeacetylas farmakologie MeSH
- jaderné proteiny genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikročipová analýza MeSH
- myši MeSH
- proteiny vázající RNA genetika MeSH
- regulace genové exprese účinky léků MeSH
- stanovení celkové genové exprese MeSH
- transfekce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
