Neuronal Yin Yang1 in the prefrontal cortex regulates transcriptional and behavioral responses to chronic stress in mice

Deborah Y. Kwon, Bing Xu, Peng Hu, Ying-Tao Zhao, Jonathan A. Beagan, Jonathan H. Nofziger, Yue Cui, Jennifer E. Phillips-Cremins, Julie A. Blendy, Hao Wu and Zhaolan Zhou ()
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Deborah Y. Kwon: University of Pennsylvania Perelman School of Medicine
Bing Xu: University of Pennsylvania
Peng Hu: University of Pennsylvania Perelman School of Medicine
Ying-Tao Zhao: University of Pennsylvania Perelman School of Medicine
Jonathan A. Beagan: University of Pennsylvania
Jonathan H. Nofziger: University of Pennsylvania Perelman School of Medicine
Yue Cui: University of Pennsylvania Perelman School of Medicine
Jennifer E. Phillips-Cremins: University of Pennsylvania
Julie A. Blendy: University of Pennsylvania Perelman School of Medicine
Hao Wu: University of Pennsylvania Perelman School of Medicine
Zhaolan Zhou: University of Pennsylvania Perelman School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Although the synaptic alterations associated with the stress-related mood disorder major depression has been well-documented, the underlying transcriptional mechanisms remain poorly understood. Here, we perform complementary bulk nuclei- and single-nucleus transcriptome profiling and map locus-specific chromatin interactions in mouse neocortex to identify the cell type-specific transcriptional changes associated with stress-induced behavioral maladaptation. We find that cortical excitatory neurons, layer 2/3 neurons in particular, are vulnerable to chronic stress and acquire signatures of gene transcription and chromatin structure associated with reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in cortical excitatory neurons enhances stress sensitivity in both male and female mice and alters the expression of stress-associated genes following an abbreviated stress exposure. These findings demonstrate how chronic stress impacts transcription in cortical excitatory neurons and identify YY1 as a regulator of stress-induced maladaptive behavior in mice.

Date: 2022
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DOI: 10.1038/s41467-021-27571-3

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