Abstract
BAHD1 is a heterochomatinization factor recently described as a component of a multiprotein complex associated with histone deacetylases HDAC1/2. The physiological and patho-physiological functions of BAHD1 are not yet well characterized. Here, we examined the consequences of BAHD1 deficiency in the brains of male mice. While Bahd1 knockout mice had no detectable defects in brain anatomy, RNA sequencing profiling revealed about 2500 deregulated genes in Bahd1-/- brains compared to Bahd1+/+ brains. A majority of these genes were involved in nervous system development and function, behavior, metabolism and immunity. Exploration of the Allen Brain Atlas and Dropviz databases, assessing gene expression in the brain, revealed that expression of the Bahd1 gene was limited to a few territories and cell subtypes, particularly in the hippocampal formation, the isocortex and the olfactory regions. The effect of partial BAHD1 deficiency on behavior was then evaluated on Bahd1 heterozygous male mice, which have no lethal or metabolic phenotypes. Bahd1+/- mice showed anxiety-like behavior and reduced prepulse inhibition (PPI) of the startle response. Altogether, these results suggest that BAHD1 plays a role in chromatin-dependent gene regulation in a subset of brain cells and support recent evidence linking genetic alteration of BAHD1 to psychiatric disorders in a human patient.
Highlights
Epifactors are nuclear proteins that play a role in epigenetic regulation of gene expression by acting on the structure of chromatin [1]
To evaluate the potential pathological changes in the brains of Bahd1-KO mutants, three histological stains were used: haematoxylin and eosin, for classic staining of the tissue structure; Periodic acid-Schiff (PAS) to label the glycoproteins; and Luxol fast blue and cresyl violet, to observe possible neuronal lesions or axon degeneration. None of these stains showed any morphological differences or aberrant cell structures in different brain sections from homozygous mutants compared with those from wild type (WT) mouse brains. Representative images of these stains in different regions of the brains of each genotype are shown in S1 Fig. Overall, no histopathological abnormality was detected in the Bahd1-KO mutant brains upon comparison with WT brains
Bromo Adjacent Homology Domain containing 1 (BAHD1) is a subunit of a chromatin-remodeling complex, whose physiological functions are not well known
Summary
Epifactors are nuclear proteins that play a role in epigenetic regulation of gene expression by acting on the structure of chromatin [1]. Epifactors are usually assembled into multiprotein complexes interacting with DNA-binding transcription factors in order to activate or repress transcription. The recruitment at specific genes and the biological function of these complexes. A role for BAHD1 in the brain d’Avenir labelled ANR-10-IDEX-0002-02, ANR-10LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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