GSE120051 H3K36 methylation and the chromodomain protein Eaf3 are required for proper co-transcriptional spliceosome assembly

Contributors : Calvin S Leung ; Stephen M Douglass ; Marco Morselli ; Matthew B Obusan ; Marat S Pavlyukov ; Matteo Pellegrini ; Tracy L JohnsonSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Saccharomyces cerevisiaeIn the eukaryotic cell, spliceosomes assemble onto pre-mRNA cotranscriptionally. The fact that spliceosome assembly takes place in the context of a dynamic chromatin environment suggests that the state of the chromatin may affect splicing. The molecular details and mechanisms through which chromatin regulates RNA splicing, however, are still unclear. Here, we show a widespread role for the histone methyltransferase Set2 and its histone modification, H3K36 methylation, in pre-mRNA splicing through high-throughput sequencing. Moreover, we find that the effect of H3K36 methylation on pre-mRNA splicing is not dependent on changes in RNA polymerase II elongation, but are driven by the chromodomain protein Eaf3. We find that Eaf3 is recruited to intron-containing genes and that Eaf3 physically interacts with the splicing factor Prp45. Eaf3 acts with Prp45 and Prp19 after formation of the pre-catalytic B complex around the time of splicing activation revealing the step in splicing that is regulated by H3K36 methylation. These studies support a model whereby H3K36 facilitates recruitment of an “adapter protein” to support efficient, constitutive splicing.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Saccharomyces cerevisiae Source Type: research