TALE-directed local modulation of H3K9 methylation shapes exon recognition

Sci Rep. 2016 Jul 21:6:29961. doi: 10.1038/srep29961.

Abstract

In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally restricted alteration of histone methylation modulates the splicing of target exons. We provide evidence that a local increase in H3K9 di- and trimethylation promotes inclusion of the target alternative exon, while demethylation by JMJD2D leads to exon skipping. We further demonstrate that H3K9me3 is localized on internal exons genome-wide suggesting a general role in splicing. Consistently, targeting of the H3K9 demethylase to a weak constitutive exon reduced co-transcriptional splicing. Together our data show H3K9 methylation within the gene body is a factor influencing recognition of both constitutive and alternative exons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Chromatin / metabolism
  • Exons / genetics*
  • Fibronectins / genetics
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Transcription Activator-Like Effectors / metabolism*
  • Transcription, Genetic

Substances

  • Chromatin
  • Fibronectins
  • Histones
  • Transcription Activator-Like Effectors
  • Lysine