Séminaire IBPS - Gene regulation by hormone receptors defines brain sex differences

En salle de conférence C404 à l'IBPS - Séminaire en anglais

Résumé du Séminaire : Gonadal steroid hormones are the principal drivers of sex-variable biology. In the brain, estrogen(17beta-estradiol)establishes neural sex differences in many vertebrates and modulates mood, behavior, and energy balance in adulthood. To understand the diverse effects of estradiol on the brain, we profiled the genomic binding of estrogen receptor alpha (ERalpha), providing the first picture of the neural actions of any gonadal hormone receptor. To understand how ERalpha target genes relate to brain sex differences we assessed gene expression in the posterior bed nucleus of the stria terminalis (BNSTp), a sexually dimorphic node in limbic circuitry that underlies sex-differential social behaviors such as aggression and parenting. 

In adult animals we observe that levels of ERalpha are predictive of the extent of sex-variable gene expression, and that these sex differences are a dynamic readout of acute hormonal state. 

In neonates we find that transient ERalpha recruitment at birth leads to persistent chromatin opening and male-biased gene expression, demonstrating a true epigenetic mechanism for brain sexual differentiation. Collectively our data identify gene programs that underlie the effects of estradiol on brain health and disease and illustrate the potential for discovery of novel gene regulatory strategies in behaviorally relevant neuronal populations.