论文部分内容阅读
Background: In the human genome, alternative splicing is a versatile mechanism to regulat gene expression at the level of precursor mRNA (pre-mRNA) processing.However, increasingly researches showed that pre-mRNA splicing is not an isolated process ; rather it is coupled with transcription and a role of this coupling is in alternative splicing regulation.Furthermore, nucleosome positioning and histone modification plays an important role in cross-talk between transcription and mRNA splicing.Some researches indicate that nucleosome positioning and histone modification may influence inclusion of internal exon sequences.Methods: Alternative exons were classified using the Astalavista framework and the Human Reference genome exons (hgl 8 database, UCSC genome browser) (Foissac & Sammeth 2007).However, as the data sets were incomplete, only 2117 skipped exons, 391 retained introns, 648 alternative acceptors, and 618 alternative donors were obtained.A total of 115,618 constitutive exons were retrieved using unique internal reference sequence (RefSeq) exons (hgl8, UCSC), removing alternative exons which include alternative events of UCSC and alternative events acquired by using the Astalavista framework with the Human Reference genome exons and mRNA exons.A genome-wide map of nucleosome positions in resting human CD4+ T cells (Schones et al.2008), Granulocytes and vitro was used (Sidow et al.2011).The genome-wide distribution of 37 histone methylations and histone acetylations as well as histone variant H2A.Z in human CD4+T cells was also used (Barski et al.2007 ; Wang et al.2008).Results: Nucleosomes are preferentially positioned within constitutive exons and/or constitutive portions of alternative exons.H2AZ, H3K4mme3 and some histone acetylations (H2BK120ac, H3K9ac, H3K18ac, H3K27ac, H4K91ac, et al) have an important role in regulating alternative donors.Conclusions: Well positioned nucleosome may serve as "speed bump" for RNAPII to facilitate recruiting splicing factors to the pre-mRNA to improve inclusion level of constitutive portions.Histone modification might serve as signals for RNAPII to recognize special splicing site.These results provided a new prospect for better appreciation of the connection between chromatin structure and gene expression regulation .