HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia‐like animals

Abstract

Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3.Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1-deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro-differentiation was almost suppressed. Neuro-differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia-like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenialike brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that coregulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro-differentiation as well as the pathophysiology of a schizophrenia-like phenotype. 530 |

Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases

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Deacetylation of Histone H4 Accompanying Cardiomyogenesis is Weakened in HDAC1-Depleted ES Cells

“…Explanted hearts were treated for 3 h in DMEM with 10% FBS, and the hearts were maintained at 37 °C in a humidified atmosphere containing 5% CO 2 . The concentrations of the HDACi were optimized in Večeřa et al [39]. …”

“…For image acquisition, we used the “tile-scanning” mode and the following objective: HCX PL APO lambda blue 20.0× 0.7 IMM UV (Leica Microsystems). Scanning was performed at a resolution of 512 × 512 pixels, and for image reconstruction, we used the auto-stitched tile-scanning mode involving the smooth-scanning mode with a slow/fine speed accuracy (set in the Leica LAS AF software connected to the Leica SP5 X microscope) [39]. …”

Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors, LET-418, SIN-3, and SPR-1 inCaenorhabditis elegansembryonic development

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