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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.12 P.1034-1044


ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells

Author(s):  Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN

Affiliation(s):  Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; more

Corresponding email(s):   litan@fudan.edu.cn

Key Words:  Apolipoprotein A-I (ApoA-I), Estrogen receptor α, (ERα, ), Acetylation of histone 3 lysine 27 (H3K27ac), p300, Breast cancer

Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN. ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells[J]. Journal of Zhejiang University Science B, 2021, 22(12): 1034-1044.

@article{title="ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells",
author="Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells
%A Bingjie WANG
%A Yinghui SHEN
%A Tianyu LIU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 12
%P 1034-1044
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100393

T1 - ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells
A1 - Bingjie WANG
A1 - Yinghui SHEN
A1 - Tianyu LIU
A1 - Li TAN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 12
SP - 1034
EP - 1044
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100393

)%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>apolipoprotein A-I (ApoA-I), the main protein component of high-density lipoprotein (HDL), plays a pivotal role in reverse cholesterol transport (RCT). Previous studies indicated a reduction of serum ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects, inhibiting cell proliferation and migration. Subsequent studies on the mechanism of expression regulation revealed that estradiol (E2)/estrogen receptor α; (ERα;) signaling activates ApoA-I gene transcription in breast cancer cells. Mechanistically, our ChIP-seq data showed that ERα directly binds to the estrogen response element (ERE) site within the ApoA-I gene and establishes an acetylation of histone 3 lysine 27 (H3K27ac)‍-enriched chromatin microenvironment. Conversely, Fulvestrant (ICI 182780) treatment blocked ERαbinding to ERE within the ApoA-I gene and downregulated the H3K27ac level on the ApoA-I gene. Treatment with p300 inhibitor also significantly decreased the ApoA-I messenger RNA (mRNA) level in MCF7 cells. Furthermore, the analysis of data from The Cancer Genome Atlas (TCGA) revealed a positive correlation between ERα and ApoA-I expression in breast cancer tissues. Taken together, our study not only revealed the antitumor potential of ApoA-I at the cellular level, but also found that ERα promotes the transcription of ApoA-I gene through direct genomic effects, and p300 may act as a co-activator of ERα in this process.




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