Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition

Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs), and that inhibition of DNA methylation results in aberrant splicing of ASEs. The methyl-CpG-binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased histone acetylation and aberrant…

• JH
  Johns Hopkins University

  Award: HCT116
• NI
  National Institutes of Health

  Award: NHLBI
• UO
  University of California, San Francisco
• NH
  National Heart, Lung, and Blood Institute