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DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease #MMPMID28827334
Jeziorska DM; Murray RJS; De Gobbi M; Gaentzsch R; Garrick D; Ayyub H; Chen T; Li E; Telenius J; Lynch M; Graham B; Smith AJH; Lund JN; Hughes JR; Higgs DR; Tufarelli C
Proc Natl Acad Sci U S A 2017[Sep]; 114 (36): E7526-35 PMID28827334show ga
The human genome contains ?30,000 CpG islands (CGIs), long stretches (0.5?2 kb) of DNA with unusually elevated levels of CpG dinucleotides. Many occur at genes' promoters, and their DNA nearly always remains unmethylated. Conversely, intragenic CGIs are often, but not always, methylated, and thus inactive as internal promoters. The mechanisms underlying these contrasting patterns of CGI methylation are poorly understood. We show that methylation of intragenic CGIs is associated with transcription running across the island. Whether or not a particular intragenic CGI becomes methylated during development depends on its transcriptional activity relative to that of the gene within which it lies. Our findings explain how intragenic CGIs are epigenetically programmed in normal development and in human diseases, including malignancy.