Journal
GENOME BIOLOGY
Volume 16, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13059-015-0797-8
Keywords
Chromatin; Splicing; Histone; Modifications; Promoters; Proximity; Transcription; Epigenetic; RNA; ENCODE
Funding
- NHGRI [1U54HG007004]
- Spanish Ministerio de Economia y Conocimiento (MINECO) [BIO2011-26205]
- ERC/European Community PF7 grant [294653]
- Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa' [SEV-2012-0208]
- Portuguese Foundation to Science and Technology [SFRH/BD/33535/2008]
- La Caixa predoctoral fellowship
- Fundacion Botin
- Banco de Santander through Santander Universities Global Division
- Consolider RNAREG
- MINECO
- AGAUR
- ICREA Funding Source: Custom
- European Research Council (ERC) [294653] Funding Source: European Research Council (ERC)
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33535/2008] Funding Source: FCT
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Background: Pre-mRNA splicing occurs mainly co-transcriptionally, and both nucleosome density and histone modifications have been proposed to play a role in splice site recognition and regulation. However, the extent and mechanisms behind this interplay remain poorly understood. Results: We use transcriptomic and epigenomic data generated by the ENCODE project to investigate the association between chromatin structure and alternative splicing. We find a strong and significant positive association between H3K9ac, H3K27ac, H3K4me3, epigenetic marks characteristic of active promoters, and exon inclusion in a small but well-defined class of exons, representing approximately 4 % of all regulated exons. These exons are systematically maintained at comparatively low levels of inclusion across cell types, but their inclusion is significantly enhanced in particular cell types when in physical proximity to active promoters. Conclusion: Histone modifications and other chromatin features that activate transcription can be co-opted to participate in the regulation of the splicing of exons that are in physical proximity to promoter regions.
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