Nuclear receptor corepressor 1 represses cardiac hypertrophy

Chao Li, Xue Nan Sun, Bo Yan Chen, Meng Ru Zeng, Lin Juan Du, Ting Liu, Hui Hui Gu, Yuan Liu, Yu Lin Li, Lu Jun Zhou, Xiao Jun Zheng, Yu Yao Zhang, Wu Chang Zhang, Yan Liu, Chaoji Shi, Shuai Shao, Xue Rui Shi, Yi Yi, Xu Liu, Jun WangJohan Auwerx, Zhao V. Wang, Feng Jia, Ruo Gu Li, Sheng Zhong Duan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine-induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy-related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.

Original languageEnglish (US)
Article numbere9127
JournalEMBO Molecular Medicine
Volume11
Issue number11
DOIs
StatePublished - Nov 7 2019

Fingerprint

Co-Repressor Proteins
Cardiomegaly
MEF2 Transcription Factors
Cardiac Myocytes
Histone Deacetylases
Hypertrophy
Pressure
Phenylephrine
Knockout Mice

Keywords

  • cardiac hypertrophy
  • class IIa HDACs
  • MEF2a
  • nuclear receptor corepressor 1

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Li, C., Sun, X. N., Chen, B. Y., Zeng, M. R., Du, L. J., Liu, T., ... Duan, S. Z. (2019). Nuclear receptor corepressor 1 represses cardiac hypertrophy. EMBO Molecular Medicine, 11(11), [e9127]. https://doi.org/10.15252/emmm.201809127

Nuclear receptor corepressor 1 represses cardiac hypertrophy. / Li, Chao; Sun, Xue Nan; Chen, Bo Yan; Zeng, Meng Ru; Du, Lin Juan; Liu, Ting; Gu, Hui Hui; Liu, Yuan; Li, Yu Lin; Zhou, Lu Jun; Zheng, Xiao Jun; Zhang, Yu Yao; Zhang, Wu Chang; Liu, Yan; Shi, Chaoji; Shao, Shuai; Shi, Xue Rui; Yi, Yi; Liu, Xu; Wang, Jun; Auwerx, Johan; Wang, Zhao V.; Jia, Feng; Li, Ruo Gu; Duan, Sheng Zhong.

In: EMBO Molecular Medicine, Vol. 11, No. 11, e9127, 07.11.2019.

Research output: Contribution to journalArticle

Li, C, Sun, XN, Chen, BY, Zeng, MR, Du, LJ, Liu, T, Gu, HH, Liu, Y, Li, YL, Zhou, LJ, Zheng, XJ, Zhang, YY, Zhang, WC, Liu, Y, Shi, C, Shao, S, Shi, XR, Yi, Y, Liu, X, Wang, J, Auwerx, J, Wang, ZV, Jia, F, Li, RG & Duan, SZ 2019, 'Nuclear receptor corepressor 1 represses cardiac hypertrophy', EMBO Molecular Medicine, vol. 11, no. 11, e9127. https://doi.org/10.15252/emmm.201809127
Li C, Sun XN, Chen BY, Zeng MR, Du LJ, Liu T et al. Nuclear receptor corepressor 1 represses cardiac hypertrophy. EMBO Molecular Medicine. 2019 Nov 7;11(11). e9127. https://doi.org/10.15252/emmm.201809127
Li, Chao ; Sun, Xue Nan ; Chen, Bo Yan ; Zeng, Meng Ru ; Du, Lin Juan ; Liu, Ting ; Gu, Hui Hui ; Liu, Yuan ; Li, Yu Lin ; Zhou, Lu Jun ; Zheng, Xiao Jun ; Zhang, Yu Yao ; Zhang, Wu Chang ; Liu, Yan ; Shi, Chaoji ; Shao, Shuai ; Shi, Xue Rui ; Yi, Yi ; Liu, Xu ; Wang, Jun ; Auwerx, Johan ; Wang, Zhao V. ; Jia, Feng ; Li, Ruo Gu ; Duan, Sheng Zhong. / Nuclear receptor corepressor 1 represses cardiac hypertrophy. In: EMBO Molecular Medicine. 2019 ; Vol. 11, No. 11.
@article{297411d7a892456fa42011124aaf780b,
title = "Nuclear receptor corepressor 1 represses cardiac hypertrophy",
abstract = "The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine-induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy-related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.",
keywords = "cardiac hypertrophy, class IIa HDACs, MEF2a, nuclear receptor corepressor 1",
author = "Chao Li and Sun, {Xue Nan} and Chen, {Bo Yan} and Zeng, {Meng Ru} and Du, {Lin Juan} and Ting Liu and Gu, {Hui Hui} and Yuan Liu and Li, {Yu Lin} and Zhou, {Lu Jun} and Zheng, {Xiao Jun} and Zhang, {Yu Yao} and Zhang, {Wu Chang} and Yan Liu and Chaoji Shi and Shuai Shao and Shi, {Xue Rui} and Yi Yi and Xu Liu and Jun Wang and Johan Auwerx and Wang, {Zhao V.} and Feng Jia and Li, {Ruo Gu} and Duan, {Sheng Zhong}",
year = "2019",
month = "11",
day = "7",
doi = "10.15252/emmm.201809127",
language = "English (US)",
volume = "11",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Nuclear receptor corepressor 1 represses cardiac hypertrophy

AU - Li, Chao

AU - Sun, Xue Nan

AU - Chen, Bo Yan

AU - Zeng, Meng Ru

AU - Du, Lin Juan

AU - Liu, Ting

AU - Gu, Hui Hui

AU - Liu, Yuan

AU - Li, Yu Lin

AU - Zhou, Lu Jun

AU - Zheng, Xiao Jun

AU - Zhang, Yu Yao

AU - Zhang, Wu Chang

AU - Liu, Yan

AU - Shi, Chaoji

AU - Shao, Shuai

AU - Shi, Xue Rui

AU - Yi, Yi

AU - Liu, Xu

AU - Wang, Jun

AU - Auwerx, Johan

AU - Wang, Zhao V.

AU - Jia, Feng

AU - Li, Ruo Gu

AU - Duan, Sheng Zhong

PY - 2019/11/7

Y1 - 2019/11/7

N2 - The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine-induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy-related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.

AB - The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine-induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy-related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.

KW - cardiac hypertrophy

KW - class IIa HDACs

KW - MEF2a

KW - nuclear receptor corepressor 1

UR - http://www.scopus.com/inward/record.url?scp=85073959594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073959594&partnerID=8YFLogxK

U2 - 10.15252/emmm.201809127

DO - 10.15252/emmm.201809127

M3 - Article

C2 - 31532577

AN - SCOPUS:85073959594

VL - 11

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 11

M1 - e9127

ER -