Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation.
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Version: Final published version
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State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_11D96B18BFB9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation.
Journal
Nucleic acids research
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
27/09/2021
Peer-reviewed
Oui
Volume
49
Number
17
Pages
9738-9754
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterize the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression, and more specifically of TET2 demethylase that may be involved in the DNA hypermethylation following short-term E2 deprivation. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER connection mainly with two partner TF families, AP-1 and FOX. These interactions take place in the proximity of E2 deprivation-mediated differentially methylated and histone acetylated enhancers. Finally, while most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation, DNA hypermethylation and H3K27 deacetylation at certain enhancers were partially retained. Overall, these results show that inactivation of ER mediates rapid and mostly reversible epigenetic changes at enhancers, and bring new insight into early events, which may ultimately lead to endocrine resistance.
Pubmed
Web of science
Open Access
Yes
Create date
12/11/2021 18:43
Last modification date
25/01/2024 8:31