title: The alternative role of DNA methylation in splicing regulation.
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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. Electronic address: galitlm@post.tau.ac.il.
authors.forename: Galit
authors.initials: G
authors.lastname: Lev Maor
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. Electronic address: ahuvyear@post.tau.ac.il.
authors.forename: Ahuvi
authors.initials: A
authors.lastname: Yearim
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. Electronic address: gilast@post.tau.ac.il.
authors.forename: Gil
authors.initials: G
authors.lastname: Ast
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000076246:CCCTC-Binding Factor; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D012326:RNA Splicing; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002868:Chromosomal Proteins, Non-Histone; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5
keywords: CpG; DNA methylation; alternative splicing; chromatin organization; histone modifications; nucleosome positioning; transcription