title: The histone variant H2A.Z is an important regulator of enhancer activity.
abstract: Gene regulatory programs in different cell types are largely defined through cell-specific enhancers activity. The histone variant H2A.Z has been shown to play important roles in transcription mainly by controlling proximal promoters, but its effect on enhancer functions remains unclear. Here, we demonstrate by genome-wide approaches that H2A.Z is present at a subset of active enhancers bound by the estrogen receptor alpha (ERα). We also determine that H2A.Z does not influence the local nucleosome positioning around ERα enhancers using ChIP sequencing at nucleosomal resolution and unsupervised pattern discovery. We further highlight that H2A.Z-enriched enhancers are associated with chromatin accessibility, H3K122ac enrichment and hypomethylated DNA. Moreover, upon estrogen stimulation, the enhancers occupied by H2A.Z produce enhancer RNAs (eRNAs), and recruit RNA polymerase II as well as RAD21, a member of the cohesin complex involved in chromatin interactions between enhancers and promoters. Importantly, their recruitment and eRNAs production are abolished by H2A.Z depletion, thereby revealing a novel functional link between H2A.Z occupancy and enhancer activity. Taken together, our findings suggest that H2A.Z acts as an important player for enhancer functions by establishing and maintaining a chromatin environment required for RNA polymerase II recruitment, eRNAs transcription and enhancer-promoters interactions, all essential attributes of enhancer activity.
authors: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada.
authors: Mylène
authors: M
authors: Brunelle
authors: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada Ontario Cancer Institute, Princess Margaret Cancer Centre/University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors: Alexei
authors: A
authors: Nordell Markovits
authors: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada.
authors: Sébastien
authors: S
authors: Rodrigue
authors: Département d'informatique, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada.
authors: Mathieu
authors: M
authors: Lupien
authors: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada Ontario Cancer Institute, Princess Margaret Cancer Centre/University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada Centre de recherche du Centre hospitalier universitaire de Sherbrooke, 12e Avenue Nord, Sherbrooke, Québec, J1H 5N4, Canada pierre-etienne.jacques@usherbrooke.ca.
authors: Pierre-Étienne
authors: http://orcid.org/0000-0002-3961-294X
authors: PÉ
authors: Jacques
authors: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 boulevard de l'Université, J1K 2R1, Sherbrooke, Québec, Canada nicolas.gevry@usherbrooke.ca.
authors: Nicolas
authors: N
authors: Gévry
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D023281:Genomics; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D061986:MCF-7 Cells; D009707:Nucleosomes / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015533:Transcriptional Activation; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004958:Estradiol; D047628:Estrogen Receptor alpha; D006657:Histones; D009707:Nucleosomes; D012319:RNA Polymerase II; D000097722:Cohesins; C077020:histone H2A.F-Z