Events

Place & date: Campus of Luminy. TAGC, Seminar room TPR2-Bloc 5. April 24 at 13h30

Title: Studying the interplay between transcription factor binding sites and DNA methylation.

 Abstract: 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 attenuate the dogma that DNA methylation is strictly associated with the heterochromatin state. Using a large set of public data, we built MethMotif, a database that records precisely TF binding sites (TFBS) along with their DNA methylation status, in a cell-specific manner. MethMotif compiles ~600 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. Overall, integrating DNA methylation to the study of transcription factor binding sites opens a new avenue for better understanding the chromatin regulation.

Selected publications:

1: Xuan Lin QX, Sian S, An O, Thieffry D, Jha S, Benoukraf T. MethMotif: an integrative cell specific database of transcription factor binding motifs coupled with DNA methylation profiles. Nucleic Acids Res. 2019 Jan 8;47(D1):D145-D154.

2: Ponnaluri VKC, Zhang G, Estève PO, Spracklin G, Sian S, Xu SY, Benoukraf T, Pradhan S. NicE-seq: high resolution open chromatin profiling. Genome Biol. 2017 Jun 28;18(1):122. 

3: Tirado-Magallanes R, Rebbani K, Lim R, Pradhan S, Benoukraf T. Whole genome DNA methylation: beyond genes silencing. Oncotarget. 2017 Jan 17;8(3):5629-5637. 

4: Adusumalli S, Mohd Omar MF, Soong R, Benoukraf T. Methodological aspects of whole-genome bisulfite sequencing analysis. Brief Bioinform. 2015 May;16(3):369-79. 

5: Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, Figueroa ME, De Figueiredo Pontes LL, Alberich-Jorda M, Zhang P, Wu M, D'Alò F, Melnick A, Leone G, Ebralidze KK, Pradhan S, Rinn JL, Tenen DG. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature. 2013 Nov 21;503(7476):371-6.

6: Benoukraf T, Wongphayak S, Hadi LH, Wu M, Soong R. GBSA: a comprehensive software for analysing whole genome bisulfite sequencing data. Nucleic Acids Res. 2013 Feb 1;41(4):e55. doi: 10.1093/nar/gks1281.