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CRE promoter sites modulate alternative splicing via p300-mediated histone acetylation
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SYSNO ASEP 0439939 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title CRE promoter sites modulate alternative splicing via p300-mediated histone acetylation Author(s) Dušková, E. (CZ)
Hnilicová, Jarmila (MBU-M) RID, ORCID
Staněk, D. (CZ)Number of authors 3 Source Title RNA biology. - : Taylor & Francis - ISSN 1547-6286
Roč. 11, č. 7 (2014), s. 1-10Number of pages 10 s. Language eng - English Country US - United States Keywords alternative splicing ; fibronectin ; p300 Subject RIV EE - Microbiology, Virology R&D Projects GBP305/12/G034 GA ČR - Czech Science Foundation (CSF) Institutional support MBU-M - RVO:61388971 UT WOS 000342901600013 DOI 10.4161/rna.29441 Annotation Histone acetylation modulates alternative splicing of several hundred genes. Here, we tested the role of the histone acetyltransferase p300 in alternative splicing and showed that knockdown of p300 promotes inclusion of the fibronectin (FN1) alternative EDB exon. p300 associates with CRE sites in the promoter via the CREB transcription factor. We created mini-gene reporters driven by an artificial promoter containing CRE sites. Both deletion and mutation of the CRE site affected EDB alternative splicing in the same manner as p300 knockdown. Next we showed that p300 controls histone H4 acetylation along the FN1 gene. Consistently, p300 depletion and CRE deletion/mutation both reduced histone H4 acetylation on mini-gene reporters. Finally, we provide evidence that the effect of CRE inactivation on H4 acetylation and alternative splicing is counteracted by the inhibition of histone deacetylases. Together, these data suggest that histone acetylation could be one of the mechanisms how promoter and promoter binding proteins influence alternative splicing Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2015
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