Histone Mods Choose Alternative Splicing Lifestyle

February 8, 2010 We can’t say we were surprised to hear that histone mods lead an alternative lifestyle—not that there’s anything wrong with that. It’s been theoretically shown that nucleosomes and their histone marks are involved in splicing by crunching data from previous experiments. Now, scientists at NCI, the University of Toronto, and the University of Texas Health Science Center have completed some more wet lab experiments to back that up, finding that histone mods directly affect alternative splicing of pre-mRNAs.

The team focused on the alternative-splicing model gene FGFR2. Depending on how the splicing and dicing goes, either exon IIIb or exon IIIc ends up in the mRNA. To map histone mods in the spliced region of this gene, the researchers used quantitative chromatin IPs. They saw that certain histone mods correlated with repression or inclusion of exon IIIb. (Lots of H3K36me3 and H3K9me1 = exon IIIb is repressed)

Then, they started toying with the system. Here are a couple of highlights:

• Changing the expression levels of SET2, which methylates H3K36, changed the splice site.
• The chromatin binding protein MRG15, which recruits splicing factors, affected splice site selection and mediated SET2’s effect on splicing.

To read more about the histone mods and their alternative splicing handiwork, check out Science, February 2010.