The alternative role of DNA methylation in splicing regulation

Galit Lev Maor*, Ahuvi Yearim, Gil Ast

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Although DNA methylation was originally thought to only affect transcription, emerging evidence shows that it also regulates alternative splicing. Exons, and especially splice sites, have higher levels of DNA methylation than flanking introns, and the splicing of about 22% of alternative exons is regulated by DNA methylation. Two different mechanisms convey DNA methylation information into the regulation of alternative splicing. The first involves modulation of the elongation rate of RNA polymerase II (Pol II) by CCCTC-binding factor (CTCF) and methyl-CpG binding protein 2 (MeCP2); the second involves the formation of a protein bridge by heterochromatin protein 1 (HP1) that recruits splicing factors onto transcribed alternative exons. These two mechanisms, however, regulate only a fraction of such events, implying that more underlying mechanisms remain to be found.

Original languageEnglish
Pages (from-to)274-280
Number of pages7
JournalTrends in Genetics
Volume31
Issue number5
DOIs
StatePublished - 1 May 2015

Keywords

  • Alternative splicing
  • Chromatin organization
  • CpG
  • DNA methylation
  • Histone modifications
  • Nucleosome positioning
  • Transcription

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