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

Kwon, D. Y., Xu, B., Hu, P., Zhao, Y.-T., Beagan, J. A., Nofziger, J. H., Cui, Y., Phillips-Cremins, J. E., Blendy, J. A., Wu, H., & Zhou, Z.

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

2022

Springer Science and Business Media LLC

Animals
Behavior, Animal
Chromatin
Epigenomics
Female
Gene Expression Regulation
Male
Metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons
Prefrontal Cortex
Stress, Physiological
YY1 Transcription Factor

English

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.

Nature Communication, Volume 13, Issue 1, January 2022, pages 1-19

The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/ by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF

Text