Regulation of Alternative Splicing by Histone Modifications

TLDR

Alternative splicing generates protein diversity, but its regulation remains poorly understood. Histone marks influence splicing by recruiting splicing regulators through a chromatin‑binding protein. Histone modifications directly regulate alternative splicing, with distinct modification signatures correlating with splicing outcomes and enabling splice site switching through an adaptor system that reads these marks.

Abstract

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.