Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function

Guangsen Shi, Pancheng Xie, Zhipeng Qu, Zhihui Zhang, Zhen Dong, Yang An, Lijuan Xing, Zhiwei Liu, Yingying Dong, Guoqiang Xu, Ling Yang, Yi Liu, Ying Xu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression.

Original languageEnglish (US)
Pages (from-to)823-834
Number of pages12
JournalCell Reports
Volume14
Issue number4
DOIs
StatePublished - Feb 2 2016

Fingerprint

Clocks
Feedback
Transcription
Cryptochromes
Chemical activation
Circadian Rhythm
Gene expression
Transcriptional Activation
Genes
Association reactions
Gene Expression
Degradation
histone deacetylase 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function. / Shi, Guangsen; Xie, Pancheng; Qu, Zhipeng; Zhang, Zhihui; Dong, Zhen; An, Yang; Xing, Lijuan; Liu, Zhiwei; Dong, Yingying; Xu, Guoqiang; Yang, Ling; Liu, Yi; Xu, Ying.

In: Cell Reports, Vol. 14, No. 4, 02.02.2016, p. 823-834.

Research output: Contribution to journalArticle

Shi, G, Xie, P, Qu, Z, Zhang, Z, Dong, Z, An, Y, Xing, L, Liu, Z, Dong, Y, Xu, G, Yang, L, Liu, Y & Xu, Y 2016, 'Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function', Cell Reports, vol. 14, no. 4, pp. 823-834. https://doi.org/10.1016/j.celrep.2015.12.076
Shi, Guangsen ; Xie, Pancheng ; Qu, Zhipeng ; Zhang, Zhihui ; Dong, Zhen ; An, Yang ; Xing, Lijuan ; Liu, Zhiwei ; Dong, Yingying ; Xu, Guoqiang ; Yang, Ling ; Liu, Yi ; Xu, Ying. / Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function. In: Cell Reports. 2016 ; Vol. 14, No. 4. pp. 823-834.
@article{85cb3a81038b4995a404e2a77cb4a341,
title = "Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function",
abstract = "In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression.",
author = "Guangsen Shi and Pancheng Xie and Zhipeng Qu and Zhihui Zhang and Zhen Dong and Yang An and Lijuan Xing and Zhiwei Liu and Yingying Dong and Guoqiang Xu and Ling Yang and Yi Liu and Ying Xu",
year = "2016",
month = "2",
day = "2",
doi = "10.1016/j.celrep.2015.12.076",
language = "English (US)",
volume = "14",
pages = "823--834",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function

AU - Shi, Guangsen

AU - Xie, Pancheng

AU - Qu, Zhipeng

AU - Zhang, Zhihui

AU - Dong, Zhen

AU - An, Yang

AU - Xing, Lijuan

AU - Liu, Zhiwei

AU - Dong, Yingying

AU - Xu, Guoqiang

AU - Yang, Ling

AU - Liu, Yi

AU - Xu, Ying

PY - 2016/2/2

Y1 - 2016/2/2

N2 - In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression.

AB - In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression.

UR - http://www.scopus.com/inward/record.url?scp=84958111948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958111948&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.12.076

DO - 10.1016/j.celrep.2015.12.076

M3 - Article

C2 - 26776516

AN - SCOPUS:84958111948

VL - 14

SP - 823

EP - 834

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 4

ER -