DHX33 Recruits Gadd45a To Cause DNA Demethylation and Regulates a Subset of Gene Transcription.

ABSTRACT: RNA helicase DHX33 was found to regulate the transcription of multiple genes involved in cancer development. But the underlying molecular mechanism remains unclear. Here, we found DHX33 associated extensively with gene promoters at CG-rich region. Its deficiency reduced the loading of active RNA polymerase II at gene promoters. Furthermore, we observed a functional interaction between DHX33, AP-2β, and DNA demethylation protein Gadd45a (growth arrest and DNA damage inductile protein 45a) at specific gene promoters. DHX33 is required to recruit GADD45a, thereby causing local DNA demethylation through further recruiting ten-eleven-translocation (Tet) methylcytosine dioxygenase enzyme, as manifested by reduced 5-hydroxymethyl cytosine levels for a subset of genes after DHX33 deficiency. This

SUBMITTER: Feng W 

PROVIDER: S-EPMC7296211 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature