BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer-Reference-Cited by-同舟云学术

BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer

Published:2022-02 Issue:6 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Liu Beibei¹,Liu Xinhua²^ORCID,Han Lulu¹,Chen Xing¹,Wu Xiaodi¹,Wu Jiajing¹,Yan Dong¹,Wang Yue¹²,Liu Shumeng¹,Shan Lin¹,Zhang Yu³,Shang Yongfeng¹²³

Affiliation:

1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China

3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China

Abstract

Significance We found that BRD4 interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers and that decommissioning BRD4-directed super-enhancer organization of transcription repression programs inflicts widespread drug resistance in breast cancer. The study uncovers a functional duality of BRD4 in super-enhancer organization of transcription activation and repression linking to oncogenesis and chemoresistance, respectively, supporting the pursuit of a combined targeting of BRD4 and PELI1 in effective treatment of breast cancer.

Funder

National Natural Science Foundation of China

Ministry of Science and Technology of the People''''s Republic of China

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2109133119

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