H2B ubiquitylation modulates spliceosome assembly and function in budding yeast

Biol Cell. 2014 Apr;106(4):126-38. doi: 10.1111/boc.201400003. Epub 2014 Feb 25.

Abstract

Background information: Commitment to splicing occurs co-transcriptionally, but a major unanswered question is the extent to which various modifications of chromatin, the template for transcription in vivo, contribute to the regulation of splicing.

Results: Here, we perform genome-wide analyses showing that inhibition of specific marks - H2B ubiquitylation, H3K4 methylation and H3K36 methylation - perturbs splicing in budding yeast, with each modification exerting gene-specific effects. Furthermore, semi-quantitative mass spectrometry on purified nuclear mRNPs and chromatin immunoprecipitation analysis on intron-containing genes indicated that H2B ubiquitylation, but not Set1-, Set2- or Dot1-dependent H3 methylation, stimulates recruitment of the early splicing factors, namely U1 and U2 snRNPs, onto nascent RNAs.

Conclusions: These results suggest that histone modifications impact splicing of distinct subsets of genes using distinct pathways.

Keywords: H2B ubiquitylation; Histone marks; Pre-mRNA Splicing; snRNP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Histones / genetics
  • Histones / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Spliceosomes / genetics
  • Spliceosomes / metabolism*
  • Ubiquitination* / genetics

Substances

  • Histones