Tues Feb 9 // Dr. Touati Benoukraf // Discipline of Genetics, Faculty of Medicine, Memorial University

Dr. Touati Benoukraf
Faculty of Medicine, Memorial University
Interplays between DNA methylation and transcription factor binding events

DNA methylation plays an essential role in gene regulation and chromatin remodeling. Accumulative evidence brought to light an interplay between the recruitment of transcription factors (TF) and DNA methylation, which attenuates the dogma that DNA methylation is strictly associated with the heterochromatin state. Using a large set of public data, we built MethMotif (http://methmotif.org), a database that records precisely TF binding sites (TFBS) along with their DNA methylation status, in a cell-specific manner. MethMotif compiles ~650 TFBS position weight matrices across 17 cell types, in human and mouse cells, computed from 2300 ChIPSeq and 23 whole-genome bisulfites sequencing (WGBS) datasets. In parallel, we launched TFRegulomeR, an R library that allows the manipulation of our data compendium. In particular, TFRegulomeR facilitates the characterization of methyl-specific transcription factor modules. Interestingly, our integrative analyses have brought to light a novel chromatin state: the primed heterochromatin, which is associated with methylated ZBTB33 binding sites. Indeed, these sites are located within condensed chromatin which is inaccessible to DNase I and Tn5 transposase and carries a newly revealed histone post-translational modification signature with significant enrichment of mono-methylation at lysine 4 of histone 3 (H3K4me1) and a complete absence of other active or expected repressive histone marks. In other words, our analyses revealed that ZBTB33 has the unique ability to bind methylated DNA across the heterochromatin, in a transition state, suggesting a potential role for ZBTB33 in heterochromatin priming.