H2B ubiquitylation modulates spliceosome assembly and function in budding yeast.
BACKGROUND
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.
Pathologie Cellulaire, University Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, Hôpital Saint Louis, Paris, Cedex 10, France.
Lucas
L
Hérissant
Erica A
EA
Moehle
Diego
D
Bertaccini
Alain
A
Van Dorsselaer
Christine
C
Schaeffer-Reiss
Christine
C
Guthrie
Catherine
C
Dargemont
D006657:Histones / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics
D006657:Histones
H2B ubiquitylation; Histone marks; Pre-mRNA Splicing; snRNP