Promoter-like epigenetic signatures in exons displaying cell type-specific splicing.
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.


CONCLUSIONS
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.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.|Graduate program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003, Porto, Portugal.
Joao
J
Curado
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.
Camilla
C
Iannone
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.|Department of Genetics, Stanford University, 300 Pasteur Dr., Stanford, CA, 94305-5120, USA.
Hagen
H
Tilgner
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain.|Institució Catalana de Recerca i Estudis Avançats, Pg Lluis Companys 23, 08010, Barcelona, Catalonia, Spain.
Juan
J
Valcárcel
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain. roderic.guigo@crg.cat.|Universitat Pompeu Fabra, Dr. Aiguader, 88, 08003, Barcelona, Catalonia, Spain. roderic.guigo@crg.cat.
Roderic
R
Guigó
D017398:Alternative Splicing; D044127:Epigenesis, Genetic; D005091:Exons; D006367:HeLa Cells; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D011401:Promoter Regions, Genetic
D006657:Histones