RGD Reference Report - Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior. - Rat Genome Database

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Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior.

Authors: Matsuda, KI  Mori, H  Nugent, BM  Pfaff, DW  McCarthy, MM  Kawata, M 
Citation: Matsuda KI, etal., Endocrinology. 2011 Jul;152(7):2760-7. doi: 10.1210/en.2011-0193. Epub 2011 May 17.
RGD ID: 7241147
Pubmed: PMID:21586557   (View Abstract at PubMed)
PMCID: PMC3115610   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2011-0193   (Journal Full-text)

Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in masculinization of the brain (estrogen receptor alpha and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide directed against the mRNA for HDAC2 and -4 in newborn male rats. Aspects of male sexual behavior in adulthood were significantly reduced by administration of either trichostatin A or antisense oligodeoxynucleotide. These results demonstrate that HDAC activity during the early postnatal period plays a crucial role in the masculinization of the brain via modifications of histone acetylation status.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of male mating behavior  IMP 7241147; 7241147 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
promoter-specific chromatin binding  IDA 7241147; 7241147 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac2  (histone deacetylase 2)
Hdac4  (histone deacetylase 4)


Additional Information