Multiple choice: how histone mods help choose where to splice

Humans can make about 100,000 different proteins with a mere 20,000 genes. How is this possible? The trick is in a process called alternative splicing, where the inclusion of different exons in mature mRNA allows the production of multiple proteins from a single gene.
The splicing machinery needs to recognise which exons to keep amongst the vast expanses of intronic sequences. So how does the splicing machinery choose where to do its job? A recent study by Luco and colleagues has proposed an answer and it involves histone modifications.
The researchers used an established model of alternative splicing, the human FGFR2 gene. The splicing that occurs in 2 different cell types leads to either exon IIIb or exon IIIc being included in the mRNA. They mapped the histone mods over the FGFR2 gene in both cell types and found that the amount of H3K36me3 was vastly increased in the cell type where exon IIIb is repressed. So the researchers tried to figure out how H3K36me3 affects the splicing outcome.
Their experiments led to the identification of a three part system made up of H3K36me3, a protein that binds to it, and the splicing regulator that represses exon IIIb.
Find out the fascinating details at http://www.sciencemag.org/cgi/content/abstract/327/5968/996

Astrid Vekemans 4239 6990