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H2B ubiquitylation modulates spliceosome assembly and function in budding yeast.

Lucas Hérissant1, Erica A Moehle, Diego Bertaccini

  • 1Pathologie Cellulaire, University Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, Hôpital Saint Louis, Paris, Cedex 10, France.

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Histone modifications like H2B ubiquitylation regulate gene splicing by influencing the recruitment of splicing factors to nascent RNA. These epigenetic marks impact distinct gene sets through specific mechanisms.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Splicing commitment is co-transcriptional.
  • The role of chromatin modifications in regulating splicing remains largely unknown.

Purpose of the Study:

  • To investigate the genome-wide impact of specific histone modifications on gene splicing.
  • To determine how histone modifications influence the recruitment of splicing factors.

Main Methods:

  • Genome-wide analyses in budding yeast.
  • Inhibition of H2B ubiquitylation, H3K4 methylation, and H3K36 methylation.
  • Semi-quantitative mass spectrometry of nuclear mRNPs.
  • Chromatin immunoprecipitation (ChIP) analysis.

Main Results:

  • Inhibition of H2B ubiquitylation, H3K4 methylation, and H3K36 methylation perturbs gene splicing in a gene-specific manner.
  • H2B ubiquitylation, but not specific H3 methylations, enhances the recruitment of U1 and U2 snRNPs to nascent RNAs.
  • These findings were observed in budding yeast.

Conclusions:

  • Histone modifications play a significant role in regulating gene splicing.
  • Different histone modifications affect distinct gene subsets through unique molecular pathways.