Seminar - Jessica Tollkuhn

Dr. Jessica Tollkuhn is pictured.
October 24, 2022 - 4:45pm
Location: 
601 Fairchild
Associate Professor
 
Host: Postdocs
 
Title: Gene regulation by hormone receptors defines brain sex differences
 
Abstract: Gonadal steroid hormones are the principal drivers of sex-variable biology. In the brain, estrogen (17β-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 (ERα), providing the first picture of the neural actions of any gonadal hormone receptor. To understand how ERα 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 ERα 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 ERα recruitment at birth leads to persistent chromatin opening and male-biased gene expression, demonstrating a true epigenetic mechanism for brain sexual differentiation. To understand the mechanistic basis of ERα target specificity, we queried our multiomic datasets to identify cluster-specfic regulators of cell type identity. We identified and validated Nfix as a “terminal selector” in a male-biased cell type and demonstrated its cooperative recruitment with ERα to a subset of target genes. 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.

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