DNA repair during Estrogen induced transcription

Estrogen-induced transcription is characterized by localized histone demethylation and DNA oxidation, followed by the recruitment of repair and DNA and histone methyl-transferase enzymes at target sites. The functional link between these different proteins recruited at estrogen chromatin sites is unclear and it is unknown which steps catalyzed by these proteins are essential for productive estrogen-mediated transcription. Here we report that specific genomic regions that synchronously recruit estrogen receptor complexed with the demethylase LSD1 and DNA repair protein such as OGG1 (a component of base excision repair) or topoisomerase II?. These enzymes are recruited at the estrogen regulatory regions in a precise temporal order and are essential for the assembly of the transcription initiation complex induced by estrogens. We find that DNA methyltransferase 3a (DNMT3a) couples BER and NER repair enzymes at promoter sites and stimulates estrogen-induced transcription initiation. The orderly recruitment of DNA and histone methyltransferases and repair enzymes greatly reduces the mutational burden induced by DNA oxidation associated with transcription.