Sex chromosome complement regulates Dnmt3a-gene expression in the anterior amygdala of developing mouse brain

SOSA, C.; CABRERA ZAPATA, L.E.; CISTERNAS, C.D.; CAMBIASSO, M.J.

Carlos Paz, Cordoba

Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Both hormonal and genetic factors interact to induce long lasting effects on sexually dimorphic gene expression in the mouse brain. Epigenetic mechanisms, such as DNA methylation, have recently been proposed as mediators of hormonal-dependent sexual differentiation of the brain. DNA methylation involves the addition of methyl groups by DNA methyltransferase enzymes (Dnmts) as well as the recruitment of methyl-binding proteins (such as MeCP2) and usually leads to gene repression. In order to study whether DNA methylation also mediates sex chromosome-dependent factors involved in sexual differentiation of the brain we used the ?four core genotypes? mouse model which allows the evaluation of gonadal sex, sex chromosome complement, and their interaction. We analyzed the mRNA expression of Dnmt3a, Dnmt1 and Mecp2 in vivo (anterior amygdala) and the interaction of hormonal and sex chromosome complement in vitro (primary neuronal cultures). Dnmt3a expression levels were higher in the anterior amygdala derived from XX embryos compared to XY, irrespectively of gonadal sex. No differences were observed in the expression of Dnmt1 and Mecp2. No significant effect of E2 or DHT on Mecp2 was seen in vitro. These results suggest that sex chromosome complement might determine a higher ?de novo DNA methylation? in specific areas of the XX brain. More experiments are required to understand the role of X/Y chromosomes in the epigenetic changes involved in the sexual differentiation of brain.