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 that correlate with the splicing
outcome in a set of human genes, and modulation of histone modifications causes
splice site switching. Histone marks affect splicing outcome by influencing the
recruitment of splicing regulators via a chromatin-binding protein. These
results outline an adaptor system for the reading of histone marks by the
pre-mRNA splicing machinery.
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