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H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription

Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER(+)) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our prev...

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Autores principales: Nagarajan, Sankari, Benito, Eva, Fischer, Andre, Johnsen, Steven A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466686/
https://www.ncbi.nlm.nih.gov/pubmed/25788266
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author Nagarajan, Sankari
Benito, Eva
Fischer, Andre
Johnsen, Steven A.
author_facet Nagarajan, Sankari
Benito, Eva
Fischer, Andre
Johnsen, Steven A.
author_sort Nagarajan, Sankari
collection PubMed
description Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER(+)) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER(+) breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers.
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spelling pubmed-44666862015-06-22 H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription Nagarajan, Sankari Benito, Eva Fischer, Andre Johnsen, Steven A. Oncotarget Research Paper Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER(+)) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER(+) breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers. Impact Journals LLC 2015-01-31 /pmc/articles/PMC4466686/ /pubmed/25788266 Text en Copyright: © 2015 Nagarajan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Nagarajan, Sankari
Benito, Eva
Fischer, Andre
Johnsen, Steven A.
H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title_full H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title_fullStr H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title_full_unstemmed H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title_short H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
title_sort h4k12ac is regulated by estrogen receptor-alpha and is associated with brd4 function and inducible transcription
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466686/
https://www.ncbi.nlm.nih.gov/pubmed/25788266
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