Super pioneer transcription factors: a new class of transcription factors that can induce DNA demethylation

Abstract

Recruitment of Transcription Factors (TFs) to regulatory regions, an essential event for transcription regulation, is hindered by the chromatin structure and by repressive epigenetic modifications. Pioneer Transcription Factors (PFs) access nucleosome-bound DNA, leading to nucleosome remodelling and chromatin opening. DNA methylation affects both access and affinity of TFs to their binding sites, thus inhibiting transcription, but it is unknown whether PFs can bind and affect DNA methylation. This project investigates PF sensitivity to and effect on DNA methylation. Most PFs do not induce changes in DNA methylation, but we identified PFs protecting from de novo DNA methylation and PFs inducing DNA demethylation around their binding sites. The latter we called “Super Pioneer Transcription Factors” (SPFs), as they are seemingly able to overcome all repressive epigenetic marks. While most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation by inhibition of the maintenance methyltransferase DNMT1 during replication.