Journal
SCIENCE
Volume 327, Issue 5968, Pages 996-1000Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1184208
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Funding
- NIH
- National Cancer Institute
- Center for Cancer Research
- National Cancer Institute of Canada
- Canadian Institutes of Health Research [MOP-67011]
- Genome Canada
- NIA/NIH [RO1 AGO32134]
- American Heart Association [0765084Y]
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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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