Title:Transcription Coupled DNA Methylation Mediated by RNA Pol II and DNMT1
VOLUME: 1 ISSUE: 2
Author(s):Mala Samaranayake, Pierre-Olivier Estève, Hang Gyeong Chin, George R. Feehery, Mihika Pradhan, Steven E. Jacobsen, Michael F. Carey and Sriharsa Pradhan
Affiliation:England Biolabs Inc., 240 County Road, Ipswich, Massachusetts 01938, USA.
Keywords:DNA methylation, DNMT1, RNA Pol II, transcription, MeCP2.
Abstract:Transcriptional gene silencing is mediated by various epigenetic modifications including
DNA methylation, histone modifications and recruitment of binding proteins that reads the methyl and
other modification marks. The order in which these modifications occur followed by repressor protein
recruitment remains contentious. Here, using purified protein components, we show that mammalian RNA polymerase II
(RNA Pol II) is involved in DNA methylation control. DNA (cytosine-5) methyltransferase 1 (DNMT1) colocalizes,
directly interacts and binds to the phosphorylated C-terminal repeat domain (CTD) of Rpb1, a major structural subunit of
RNA Pol II. The association of RNA Pol II with DNMT1 during transcription enhances DNA methylation, and
methylated DNA doesn’t affect in vitro transcription. Addition of methyl CpG binding protein 2 (MeCP2), inhibited in
vitro transcription of DNA in a methylation dependent manner, suggesting a possible mechanism for RNA Pol II coupled
transcriptional silencing mediated by DNMT1 and MeCP2.
