Gene regulation by gonadal hormone receptors underlies brain sex differences

Gegenhuber, B, Wu, MV, Bronstein, R, Tollkuhn, J (May 2022) Gene regulation by gonadal hormone receptors underlies brain sex differences. Nature. ISSN 0028-0836

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Abstract

<jats:title>Abstract</jats:title><jats:p>Oestradiol establishes neural sex differences in many vertebrates<jats:sup>1–3</jats:sup> and modulates mood, behaviour and energy balance in adulthood<jats:sup>4–8</jats:sup>. In the canonical pathway, oestradiol exerts its effects through the transcription factor oestrogen receptor-α (ERα)<jats:sup>9</jats:sup>. Although ERα has been extensively characterized in breast cancer, the neuronal targets of ERα, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERα-binding sites in a sexually dimorphic neural circuit that mediates social behaviours. We conclude that ERα orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of oestradiol on brain development, behaviour and disease.</jats:p>

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > hormones neurobiology > neuroanatomy organism description > animal behavior > sex differences
CSHL Authors:	Gegenhuber, Bruno Wu, Melody Bronstein, Robert Tollkuhn, Jessica
Communities:	CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service CSHL Cancer Center Shared Resources > Single-Cell Biology Service CSHL labs > Tollkuhn lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	4 May 2022
Date Deposited:	17 May 2022 14:41
Last Modified:	02 May 2024 15:52
PMCID:	PMC9159952
URI:	https://repository.cshl.edu/id/eprint/40609

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