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

Sankari Nagarajan, Eva Benito, Andre Fischer, Steven Johnsen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7305-7317
Number of pages13
JournalOncotarget
Volume6
Issue number9
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Estrogen Receptor alpha
Estrogens
Proteins
Hormones
Histone Code
Breast Neoplasms
Genes
Gene Expression
Chromatin Assembly and Disassembly
Transcription Initiation Site
Acetylation
Protein Binding
Epigenomics
Estrogen Receptors
Histones
Lysine
Binding Sites
Genome
RNA
Neoplasms

Keywords

  • Bromodomain
  • Chromatin
  • Epigenetics
  • Estrogen
  • Histone acetylation

ASJC Scopus subject areas

  • Oncology

Cite this

H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription. / Nagarajan, Sankari; Benito, Eva; Fischer, Andre; Johnsen, Steven.

In: Oncotarget, Vol. 6, No. 9, 01.01.2015, p. 7305-7317.

Research output: Contribution to journalArticle

Nagarajan, Sankari ; Benito, Eva ; Fischer, Andre ; Johnsen, Steven. / H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription. In: Oncotarget. 2015 ; Vol. 6, No. 9. pp. 7305-7317.
@article{faaa8492b5474c12b6f57ce8c3f9d129,
title = "H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription",
abstract = "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.",
keywords = "Bromodomain, Chromatin, Epigenetics, Estrogen, Histone acetylation",
author = "Sankari Nagarajan and Eva Benito and Andre Fischer and Steven Johnsen",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.3439",
language = "English (US)",
volume = "6",
pages = "7305--7317",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "9",

}

TY - JOUR

T1 - H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription

AU - Nagarajan, Sankari

AU - Benito, Eva

AU - Fischer, Andre

AU - Johnsen, Steven

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Bromodomain

KW - Chromatin

KW - Epigenetics

KW - Estrogen

KW - Histone acetylation

UR - http://www.scopus.com/inward/record.url?scp=84927153498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927153498&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.3439

DO - 10.18632/oncotarget.3439

M3 - Article

C2 - 25788266

AN - SCOPUS:84927153498

VL - 6

SP - 7305

EP - 7317

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 9

ER -