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The histone variant H2A.Z is an important regulator of enhancer activity

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 de...

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Autores principales: Brunelle, Mylène, Nordell Markovits, Alexei, Rodrigue, Sébastien, Lupien, Mathieu, Jacques, Pierre-Étienne, Gévry, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787790/
https://www.ncbi.nlm.nih.gov/pubmed/26319018
http://dx.doi.org/10.1093/nar/gkv825
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author Brunelle, Mylène
Nordell Markovits, Alexei
Rodrigue, Sébastien
Lupien, Mathieu
Jacques, Pierre-Étienne
Gévry, Nicolas
author_facet Brunelle, Mylène
Nordell Markovits, Alexei
Rodrigue, Sébastien
Lupien, Mathieu
Jacques, Pierre-Étienne
Gévry, Nicolas
author_sort Brunelle, Mylène
collection PubMed
description 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.
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spelling pubmed-47877902016-03-14 The histone variant H2A.Z is an important regulator of enhancer activity Brunelle, Mylène Nordell Markovits, Alexei Rodrigue, Sébastien Lupien, Mathieu Jacques, Pierre-Étienne Gévry, Nicolas Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2015-11-16 2015-08-28 /pmc/articles/PMC4787790/ /pubmed/26319018 http://dx.doi.org/10.1093/nar/gkv825 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Brunelle, Mylène
Nordell Markovits, Alexei
Rodrigue, Sébastien
Lupien, Mathieu
Jacques, Pierre-Étienne
Gévry, Nicolas
The histone variant H2A.Z is an important regulator of enhancer activity
title The histone variant H2A.Z is an important regulator of enhancer activity
title_full The histone variant H2A.Z is an important regulator of enhancer activity
title_fullStr The histone variant H2A.Z is an important regulator of enhancer activity
title_full_unstemmed The histone variant H2A.Z is an important regulator of enhancer activity
title_short The histone variant H2A.Z is an important regulator of enhancer activity
title_sort histone variant h2a.z is an important regulator of enhancer activity
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787790/
https://www.ncbi.nlm.nih.gov/pubmed/26319018
http://dx.doi.org/10.1093/nar/gkv825
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