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Regulation of neural gene expression by estrogen receptor alpha

View ORCID ProfileBruno Gegenhuber, View ORCID ProfileMelody V. Wu, Robert Bronstein, View ORCID ProfileJessica Tollkuhn
doi: https://doi.org/10.1101/2020.10.21.349290
Bruno Gegenhuber
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
2Cold Spring Harbor Laboratory School of Biological Sciences, Cold Spring Harbor, NY 11724 USA
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Melody V. Wu
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Robert Bronstein
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Jessica Tollkuhn
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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  • For correspondence: tollkuhn@cshl.edu
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Abstract

The transcription factor estrogen receptor α (ERα) is a principal regulator of sex differences in the vertebrate brain and can modulate mood, behavior, and energy balance in females and males. However, the genes regulated by ERα in the brain remain largely unknown. Here we reveal the genomic binding of ERα within a sexually dimorphic neural circuit that regulates social behaviors. We profiled gene expression and chromatin accessibility and show ERα induces a neurodevelopmental gene program in adulthood. We further demonstrate that ERα binds with Nuclear factor I X-type (Nfix) to regulate a male-biased gene expression program that initiates in early life. Our results reveal a neural strategy for ERα-mediated gene regulation and provide molecular targets that underlie estrogen’s effects on brain development, behavior, and disease.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 21, 2020.
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Regulation of neural gene expression by estrogen receptor alpha
Bruno Gegenhuber, Melody V. Wu, Robert Bronstein, Jessica Tollkuhn
bioRxiv 2020.10.21.349290; doi: https://doi.org/10.1101/2020.10.21.349290
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Regulation of neural gene expression by estrogen receptor alpha
Bruno Gegenhuber, Melody V. Wu, Robert Bronstein, Jessica Tollkuhn
bioRxiv 2020.10.21.349290; doi: https://doi.org/10.1101/2020.10.21.349290

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