GADD45A binds R-loops and recruits TET1 to CpG island promoters.

ABSTRACT: R-loops are DNA-RNA hybrids enriched at CpG islands (CGIs) that can regulate chromatin states^1-8. How R-loops are recognized and interpreted by specific epigenetic readers is unknown. Here we show that GADD45A (growth arrest and DNA damage protein 45A) binds directly to R-loops and mediates local DNA demethylation by recruiting TET1 (ten-eleven translocation 1). Studying the tumor suppressor TCF21 (ref. ⁹), we find that antisense long noncoding (lncRNA) TARID (TCF21 antisense RNA inducing promoter demethylation) forms an R-loop at the TCF21 promoter. Binding of GADD45A to the R-loop triggers local DNA demethylation and TCF21 expression. TARID transcription, R-loop formation, DNA demethylation, and TCF21 expression proceed sequentially during the cell cycle. Oxidized D

SUBMITTER: Arab K 

PROVIDER: S-EPMC6420098 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature