Project description:Histone deacetylase 3 (HDAC3) is unique among the HDAC superfamily of chromatin modifiers that silence transcription through enzymatic modification of histones, because interaction with nuclear receptor corepressors (NCoR1/2) is required for engagement of its catalytic activity. However, loss of HDAC3 also represses transcription. Here we report that, during lipopolysaccharide (LPS) activation of macrophages, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound enhancers that repress anti-inflammatory genes. By contrast, LPS-stimulated recruitment of HDAC3 to ATF2-bound sites without NCoR1/2 activates pro-inflammatory genes by a non-canonical mechanism whereby catalytically inactive HDAC3 stably interacts with p65. Consistent with this bimodal inflammatory modulation, deletion of HDAC3 in macrophages safeguards mice from lethal exposure to LPS, but this protection is not conferred by genetic or pharmacological abolition of HDAC3 catalytic activity. Thus, HDAC3 is a dichotomous transcriptional activator and repressor whose deacetylase-independent functions are critical in priming the innate immune system.

2020-04-30 | GSE140610 | GEO

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [ChIP-Seq]

2020-04-30 | GSE140581 | GEO

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [GRO-Seq]

2020-04-30 | GSE140573 | GEO

Dichotomous engagement of HDAC3 activity governs inflammatory responses.

Project description: Not available

| S-EPMC7725280 | biostudies-literature

Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-30 | GSE140611 | GEO

HDAC3 requirement for the inflammatory gene expression program in macrophages

Project description:This SuperSeries is composed of the following subset Series: GSE33162: HDAC3 requirement for the inflammatory gene expression program in macrophages [gene expression] GSE33163: HDAC3 requirement for the inflammatory gene expression program in macrophages [ChIP_Seq] Refer to individual Series

2012-07-08 | E-GEOD-33164 | biostudies-arrayexpress

Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo

Project description:Histone deacetylase 3 (HDAC3) is an epigenome-modifying enzyme that is required for normal mouse development and tissue-specific functions. In vitro, HDAC3 protein itself has minimal enzyme activity, but gains its histone deacetylation function from stable association with the conserved deacetylase activation domain (DAD) contained in nuclear receptor corepressors NCOR1 and SMRT. Here we show that HDAC3 enzyme activity is undetectable in mice bearing point mutations in the DAD of both NCOR1 and SMRT (NS-DADm), despite normal levels of HDAC3 protein. Local histone acetylation is increased, and genomic HDAC3 recruitment is reduced though not abrogated. Remarkably, the NS-DADm mice are born and live to adulthood, whereas genetic deletion of HDAC3 is embryonic lethal. These findings demonstrate that nuclear receptor corepressors are required for HDAC3 enzyme activity in vivo, and suggest that a deacetylase-independent function of HDAC3 may be required for life. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.

2013-01-01 | E-GEOD-42541 | biostudies-arrayexpress

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