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Status |
Public on Jan 01, 2013 |
Title |
Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Refer to individual Series.
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Citation(s) |
23292142 |
Submission date |
Nov 27, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Hee-Woong Lim |
Organization name |
Cincinnati Children's Hospital Medical Center
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Department |
Division of Biomedical Informatics
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Street address |
3333 Burnet Ave. MLC 7024
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City |
Cincinnati |
State/province |
Ohio |
ZIP/Postal code |
45229 |
Country |
USA |
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Platforms (2) |
GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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Samples (11)
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This SuperSeries is composed of the following SubSeries: |
GSE42537 |
Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo (Microarray) |
GSE42540 |
Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo (ChIP-Seq) |
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Relations |
BioProject |
PRJNA182231 |