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.