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

• Published in: Nature communications 2022-01, Vol.13 (1), p.55-55, Article 55
• Main Authors: Kwon, Deborah Y., Xu, Bing, Hu, Peng, Zhao, Ying-Tao, Beagan, Jonathan A., Nofziger, Jonathan H., Cui, Yue, Phillips-Cremins, Jennifer E., Blendy, Julie A., Wu, Hao, Zhou, Zhaolan
• Format: Article
• Language: English
• Subjects: 38; 38/91; 631/208/200; 631/378/1689/1831; 631/378/2584/2585; 64; 64/60; Ablation; Animals; Behavior; Behavior, Animal; Cerebral cortex; Chromatin; Chromatin - metabolism; Epigenomics; Female; Gene expression; Gene Expression Regulation; Humanities and Social Sciences; Male; Mental depression; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Neocortex; Neurons; Neurons - metabolism; Prefrontal cortex; Prefrontal Cortex - metabolism; Science; Science (multidisciplinary); Sensitivity enhancement; Stress; Stress, Physiological; Transcription; Transcriptomes; YY1 protein; YY1 Transcription Factor - genetics; YY1 Transcription Factor - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27571-3

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. The mechanisms underlying the chronic stress-induced increased risk for major depressive disorder and anxiety are unclear. Here, the authors show the transcriptional changes occurring in neocortical neurons and identify YY1 as a regulator of chronic stress-induced maladaptive behavior in mice.