National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2010 Feb 19;327(5968):996-1000. doi: 10.1126/science.1184208. Epub 2010 Feb 4.
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.
前体 mRNA 的可变剪接是产生蛋白质多样性的主要机制，但对其调控机制了解甚少。我们证明了组蛋白修饰在可变剪接中的直接作用。我们发现了在一组人类基因中与剪接结果相关的独特组蛋白修饰特征，并发现组蛋白修饰的调节会导致剪接位点的转换。组蛋白标记通过影响剪接调节因子通过染色质结合蛋白的募集来影响剪接结果。这些结果概述了一个适体系统，用于前体 mRNA 剪接机制读取组蛋白标记。
