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.
Biol Cell. 2014 Apr;106(4):126-38. doi: 10.1111/boc.201400003. Epub 2014 Feb 25.
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.
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.
These results suggest that histone modifications impact splicing of distinct subsets of genes using distinct pathways.
剪接的发生是共转录的，但一个尚未解决的主要问题是，染色质的各种修饰（转录的模板）在多大程度上有助于剪接的调节。
在这里，我们进行了全基因组分析，结果表明，抑制特定标记 - H2B 泛素化、H3K4 甲基化和 H3K36 甲基化 - 会干扰芽殖酵母中的剪接，每种修饰都具有基因特异性的影响。此外，对纯化核 mRNPs 的半定量质谱分析和内含子基因的染色质免疫沉淀分析表明，H2B 泛素化，而不是 Set1、Set2 或 Dot1 依赖性 H3 甲基化，会刺激早期剪接因子，即 U1 和 U2 snRNPs，招募到新生 RNA 上。
这些结果表明，组蛋白修饰通过不同的途径影响不同亚群基因的剪接。
