Regulation of Alternative Splicing by Histone Modifications

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Science  04 Feb 2010:
DOI: 10.1126/science.1184208


Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing. We found distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. Histone marks affect splicing outcome by directly modulating the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery.