The protein encoded by MECP2 interacts with the NCoR/HDAC3 complex; the Rett syndrome-associated missense variant p.Arg306Cys (MECP2R306C) abolishes this interaction (Lyst et al., 2013; Ebert et al., 2013). Knockdown of HDAC3 in the forebrain excitatory neurons of mice resulted in abnormal locomotor coordination, social deficits, and cognitive deficits (Nott et al., 2016). In the same report, Rett syndrome patient-derived MECP2R306C neural progenitor cells were shown to have deficits in HDAC3 recruitment. A de novo in-frame deletion variant in HDAC3 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).
Molecular Function
The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family; it has histone deacetylase activity and represses transcription when tethered to a promoter.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 11-14 of Hdac3 using CamkII-cre, in excitatory neurons of the forebrain
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Unreported
Mutant ES Cell Line: 129SvEv-derived ES cells
Model Source:
Description: Hdac3 cko mice show increased activity compared to wt mice
Exp Paradigm: Control and male hdac3 cko mice were subjectedto the open-field test for 60 min and analyzed in 5-min bins for timespent in the center
Description: Hdac3 cko mice showed impaired motor coordination compared to wt mice
Exp Paradigm: Each mouse performed two consecutive 5 min trials with an inter-trial interval of 10 min
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Hdac3 cko mice showed reduced freezing in the conditioning chamber compared to wt mice
Exp Paradigm: The test measures freezing in response to the context of the conditioning chamber
Description: Hdac3 cko mice took similar durations to reach the platform on days 6 and 7 whereas wt mice displayed spatial learning as reduced latency to reach the platform by days 6 and 7
Exp Paradigm: Mice are required to locate a hidden platform in an opaque pool of water using visual cues
Description: Hdac3 cko mice showed impaired suppression of contextual and cued memory recall compared to wt mice
Exp Paradigm: The test compares activity before the shock with activity during testing
Description: Hdac3 cko mice spent similar durations exploring both the novel and familiar locations of the object whereas wt mice spent more time at the novel location
Exp Paradigm: Mice were trained to the position of two identical objects and later one object was repositioned
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Hdac3 cko mice showed reduced freezing to the auditory cue compared to wt mice
Exp Paradigm: The test measures freezing in response to the auditory cue
Description: Hdac3 cko mice showed reduced time in the target quadrant and a low number of passes through the platform location compared to wt mice
Exp Paradigm: Mice are required to locate a hidden platform in an opaque pool of water using visual cues, probe trial was conducted 24 h after the last training session (day 8) when the platform was removed
Description: Hdac3 cko mice showed no expression of hdac3 in hippocampal and cortical neurons compared to wt mice that showed normal expression of hdac3 in hippocampal and cortical neurons
Exp Paradigm: The ca1 was isolated from the hippocampus of male mice- western blot: hippocampus
Description: Hdac3 cko mice showed down-regulated expressions of 194 of 303 genes compared to wt mice, genes down-regulated in hdac3 mice included immediate-early genes ( arc, fos, nov, bdnf and nr4a1), the synaptic genes (gabra5, chrna5 and doc2b) and arrdc2, dusp4, klf10, tle1 and adcyap1,
Exp Paradigm: Rna-seq in the ca1 area of the hippocampus, a region enriched for neurons with deletion of hdac3-rna sequencing: hippocampus ca1 region
Description: Hdac3 cko mice showed decreased fos protein in the ca1 pyramidal cell layer of the hippocampus compared to wt mice
Exp Paradigm: Immunohistochemistry: hippocampus ca1 region; western blot: hippocampus ca1 region;- western blot: hippocampus ca1 region
Description: Hdac3 cko mice showed no expression of hdac3 in hippocampal and cortical neurons compared to wt mice that showed normal expression of hdac3 in hippocampal and cortical neurons
Exp Paradigm: The ca1 was isolated from the hippocampus of male mice- rna sequencing
Description: Hdac3 cko mice showed down-regulated expressions of 194 of 303 genes compared to wt mice, genes down-regulated in hdac3 mice included immediate-early genes ( arc, fos, nov, bdnf and nr4a1), the synaptic genes (gabra5, chrna5 and doc2b) and arrdc2, dusp4, klf10, tle1 and adcyap1,
Exp Paradigm: Rna-seq in the ca1 area of the hippocampus, a region enriched for neurons with deletion of hdac3- quantitative pcr (qrt-pcr): hippocampus ca1 region
Description: Hdac3 cko mice showed increased snap25 protein in the ca1 region of the hippocampus compared to wt mice
Exp Paradigm: Immunohistochemistry: hippocampus ca1 region; western blot: hippocampus ca1 region;-immunohistochemistry: hippocampus ca1 region
Description: Hdac3 cko mice showed upregulated expressions of 109 of 303 genes compared to wt mice, upregulated genes were involved in synaptic transmission (snap25, nrgn and ppp1r1b), neurological system process and transmission of nerve impulse
Exp Paradigm: Rna-seq in the ca1 area of the hippocampus, a region enriched for neurons with deletion of hdac3-rna sequencing: hippocampus ca1 region
Description: Hdac3 cko mice showed no expression of hdac3 in hippocampal and cortical neurons compared to wt mice that showed normal expression of hdac3 in hippocampal and cortical neurons
Exp Paradigm: The ca1 was isolated from the hippocampus of male mice- quantitative pcr (qrt-pcr)
Description: Hdac3 cko mice showed down-regulated expressions of 194 of 303 genes compared to wt mice, genes down-regulated in hdac3 mice included immediate-early genes ( arc, fos, nov, bdnf and nr4a1), the synaptic genes (gabra5, chrna5 and doc2b) and arrdc2, dusp4, klf10, tle1 and adcyap1,
Exp Paradigm: Rna-seq in the ca1 area of the hippocampus, a region enriched for neurons with deletion of hdac3- immunohistochemistry: hippocampus ca1 region
Description: Hdac3 cko mice showed increased snap25 protein in the ca1 region of the hippocampus compared to wt mice
Exp Paradigm: Immunohistochemistry: hippocampus ca1 region; western blot: hippocampus ca1 region;- western blot: hippocampus ca1 region
Description: Hdac3 cko mice showed no expression of hdac3 in hippocampal and cortical neurons compared to wt mice that showed normal expression of hdac3 in hippocampal and cortical neurons
Exp Paradigm: The ca1 was isolated from the hippocampus of male mice-immunohistochemistry: hippocampus
Description: Hdac3 cko mice showed upregulated expressions of 109 of 303 genes compared to wt mice, upregulated genes were involved in synaptic transmission (snap25, nrgn and ppp1r1b), neurological system process and transmission of nerve impulse
Exp Paradigm: Rna-seq in the ca1 area of the hippocampus, a region enriched for neurons with deletion of hdac3- quantitative pcr (qrt-pcr): hippocampus ca1 region
Description: Hdac3 cko mice showed decreased binding of hdac3 at the regulatory regions of the genes, arrdc2, dusp4, klf10, tle1, bdnf and nr4a1 compared to wt controls
Exp Paradigm: Chromatin immunoprecipitation sequencing (chip-seq): hippocampus;
Description: Hdac3 cko mice showed decreased fos protein in the ca1 pyramidal cell layer of the hippocampus compared to wt mice
Exp Paradigm: Immunohistochemistry: hippocampus ca1 region; western blot: hippocampus ca1 region;-immunohistochemistry: hippocampus ca1 region
