The histone variant macroH2A1.1 regulates RNA Polymerase II paused genes within defined chromatin interaction landscapes.
Fiche publication
Date publication
avril 2022
Journal
Journal of cell science
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Recoules L, Heurteau A, Raynal F, Karasu N, Moutahir F, Bejjani F, Jariel-Encontre I, Cuvier O, Sexton T, Lavigne AC, Bystricky K
Lien Pubmed
Résumé
The histone variant macroH2A1.1 plays a role in cancer development and metastasis. To determine the underlying molecular mechanisms, we mapped the genome-wide localization of endogenous macroH2A1.1 in the human breast cancer cell line MDA-MB 231. We demonstrate that macroH2A1.1 specifically binds to active promoters and enhancers in addition to facultative heterochromatin. Selective knock-down of macroH2A1.1 deregulates expression of hundreds of highly active genes. Depending on the chromatin landscape, macroH2A1.1 acts through two distinct molecular mechanisms. The first mitigates excessive transcription by binding over domains including the promoter and the gene body. The second stimulates expression of RNA Polymerase II (Pol II) paused genes, including genes regulating mammary tumor cell migration. In contrast to the first one, macroH2A1.1 specifically associates with the TSS of Pol II paused genes. These processes occur in a predefined local 3D genome landscape but do not require rewiring of enhancer-promoter contacts. We thus propose that macroH2A1.1 serves as a transcriptional modulator with a potential role in assisting the conversion of promoter-locked into a productive and elongating Pol II.
Mots clés
Breast cancer, Cellular migration, Chromatin structure, Gene expression, Histone variants, RNA Polymerase II paused genes
Référence
J Cell Sci. 2022 Apr 1;: