Targeting of N-CoR and histone deacetylase 3 by the oncoprotein v-ErbA yields a chromatin infrastructure-dependent transcriptional repression pathway

ABSTRACT Nuclear receptor corepressors (N-CoR) and silencing mediator for retinoid and thyroid receptors (SMRT) have both been implicated in thyroid hormone receptor (TR)-mediated repression. Here we show that endogenous N-CoR, TBL1, and histone deacetylase 3 (HDAC3), but not HDAC1, -2, or -4, are recruited to a stably integrated reporter gene repressed by unliganded TR as well as the orphan receptor RevErb. Unliganded TR also recruits this complex to a transiently transfected reporter, and transcriptional repression is associated with local histone deacetylation that is reversed by the presence of thyroid hormone. Knockdown of N-CoR using small interfering RNAs markedly reduces repression by the TR ligand binding domain in human 293T cells, whereas knockdown of SMRT has little effect. RevErb repression appears to involve both corepressors in this system. Knockdown of HDAC3 markedly reduces repression by both TR and RevErb, while knockdown of HDAC1 or 2 has more modest, partly nonspecific effects. Thus, HDAC3 is critical for repression by multiple nuclear receptors and the N-CoR HDAC3 complex plays a unique and necessary role in TR-mediated gene repression in human 293T cells.

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Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

FEBS Letters ◽

10.1016/j.febslet.2010.03.048 ◽

2010 ◽

Vol 584 (11) ◽

pp. 2225-2230 ◽

Cited By ~ 11

Author(s):

Jung-Yoon Yoo ◽

Kyung-Chul Choi ◽

HeeBum Kang ◽

Young Jun Kim ◽

Jeongmin Lee ◽

...

Keyword(s):

Histone Deacetylase ◽

Transcriptional Repression ◽

Histone Deacetylase 3

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Contribution of HDAC3 to transcriptional repression by the human papillomavirus 31 E8^E2 protein

Journal of General Virology ◽

10.1099/jgv.0.001438 ◽

2020 ◽

Vol 101 (7) ◽

pp. 751-759

Author(s):

Marcel Dreer ◽

Saskia Blondzik ◽

Elke Straub ◽

Thomas Iftner ◽

Frank Stubenrauch

Keyword(s):

Transcription Factors ◽

Human Papillomavirus ◽

Histone Deacetylase ◽

Transcriptional Repression ◽

Human Papillomaviruses ◽

Related Protein ◽

E2 Protein ◽

Histone Deacetylase 3 ◽

Cellular Genes ◽

Cellular Transcription

Human papillomaviruses (HPV) such as HPV16 and HPV31 encode an E8^E2 protein that acts as a repressor of viral replication and transcription. E8^E2′s repression activities are mediated via the interaction with host-cell NCoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoid and thyroid receptors) corepressor complexes, which consist of NCoR, its homologue SMRT, GPS2 (G-protein pathway suppressor 2), HDAC3 (histone deacetylase 3), TBL1 (transducin b-like protein 1) and its homologue TBLR1 (TBL1-related protein 1). We now provide evidence that transcriptional repression by HPV31 E8^E2 is NCoR/SMRT-dependent but surprisingly always HDAC3-independent when analysing different HPV promoters. This is in contrast to the majority of several cellular transcription factors using NCoR/SMRT complexes whose transcriptional repression activities are both NCoR/SMRT- and HDAC3-dependent. However, NCoR/SMRT-dependent but HDAC3-independent repression has been described for specific cellular genes, suggesting that this may not be specific for HPV promoters but could be a feature of a subset of NCoR/SMRT-HDAC3 regulated genes.

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Transcriptional Repression of Histone Deacetylase 3 by the Histone Demethylase KDM2A Is Coupled to Tumorigenicity of Lung Cancer Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m113.521625 ◽

2014 ◽

Vol 289 (11) ◽

pp. 7483-7496 ◽

Cited By ~ 35

Author(s):

Shilpa S. Dhar ◽

Hunain Alam ◽

Na Li ◽

Klaus W. Wagner ◽

Jimyung Chung ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Histone Deacetylase ◽

Transcriptional Repression ◽

Histone Demethylase ◽

Lung Cancer Cells ◽

Histone Deacetylase 3

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The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

Cell Death and Disease ◽

10.1038/s41419-021-04019-6 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Li Ning ◽

Xiong Rui ◽

Wang Bo ◽

Geng Qing

Keyword(s):

Histone Deacetylase ◽

Chromatin Remodeling ◽

Current Knowledge ◽

Organ Injury ◽

Solid Organ ◽

Solid Organ Injury ◽

Histone Deacetylase 3 ◽

Physiological Conditions ◽

Inflammatory Conditions ◽

Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

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