Regulation of Alternative Splicing by Histone Modifications

Histones and Alternative Splicing

Alternative splicing—the inclusion of different combinations of gene exons within a messenger RNA transcript—occurs in the majority of human genes and is regulated by basal and tissue-specific splicing factors, by transcription kinetics, and by chromatin structure. Luco et al. (p. 996 , published online 4 February) analyzed the alternative splicing of the human fibroblast growth factor receptor 2 gene in tissue culture cells and found that inclusion of exon IIIb or IIIc was modulated by the levels of histone H3 lysine 36 trimethylation (H3-K36me3) and H3-K4me3. Histone H3-K36me3 enrichment correlated with binding of the chromatin protein, MRG15. The MRG15 protein in turn recruited the polypyrimidine tract–binding protein (PTB) splicing factor, which acts to repress alternative exon inclusion, thus establishing a direct link between histone modifications and the splicing machinery.