A signalling pathway for transcriptional regulation of sleep amount in mice

作者全名："Zhou, Rui; Wang, Guodong; Li, Qi; Meng, Fanxi; Liu, Can; Gan, Rui; Ju, Dapeng; Liao, Meimei; Xu, Junjie; Sang, Di; Gao, Xue; Zhou, Shuang; Wu, Kejia; Sun, Quanzhi; Guo, Ying; Wu, Chongyang; Chen, Zhiyu; Chen, Lin; Shi, Bihan; Wang, Haiyan; Wang, Xia; Li, Huaiye; Cai, Tao; Li, Bin; Wang, Fengchao; Funato, Hiromasa; Yanagisawa, Masashi; Zhang, Eric Erquan; Liu, Qinghua"

作者地址："[Zhou, Rui; Liao, Meimei] China Agr Univ, Coll Biol Sci, Beijing, Peoples R China; [Zhou, Rui; Wang, Guodong; Li, Qi; Meng, Fanxi; Liu, Can; Gan, Rui; Liao, Meimei; Xu, Junjie; Sang, Di; Gao, Xue; Zhou, Shuang; Wu, Kejia; Sun, Quanzhi; Guo, Ying; Wu, Chongyang; Chen, Zhiyu; Chen, Lin; Shi, Bihan; Wang, Haiyan; Wang, Xia; Li, Huaiye; Cai, Tao; Li, Bin; Wang, Fengchao; Zhang, Eric Erquan; Liu, Qinghua] Natl Inst Biol Sci, Beijing NIBS, Beijing, Peoples R China; [Wang, Guodong; Meng, Fanxi; Sang, Di] Chinese Acad Med Sci, Grad Sch, Peking Union Med Coll, Beijing, Peoples R China; [Li, Qi; Cai, Tao; Wang, Fengchao; Zhang, Eric Erquan; Liu, Qinghua] Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res TIMBR, Beijing, Peoples R China; [Liu, Can] Tsinghua Univ, Peking Univ Tsinghua Univ NIBS Joint Grad Program, Sch Life Sci, Beijing, Peoples R China; [Ju, Dapeng] Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing, Peoples R China; [Xu, Junjie; Zhou, Shuang] Beijing Normal Univ, Coll Life Sci, Beijing, Peoples R China; [Funato, Hiromasa] Toho Univ, Fac Med, Dept Anat, Tokyo, Japan; [Funato, Hiromasa; Yanagisawa, Masashi; Liu, Qinghua] Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki, Japan"

通信作者："Liu, QH (通讯作者)，Natl Inst Biol Sci, Beijing NIBS, Beijing, Peoples R China.; Liu, QH (通讯作者)，Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res TIMBR, Beijing, Peoples R China.; Liu, QH (通讯作者)，Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki, Japan."

来源：NATURE

ESI学科分类：Multidisciplinary

WOS号：WOS:000895213100001

JCR分区：Q1

影响因子：64.8

年份：2022

卷号：612

期号：7940

开始页：519

结束页：+

文献类型：Article

关键词：　

摘要："In mice and humans, sleep quantity is governed by genetic factors and exhibits age-dependent variation(1-3). However, the core molecular pathways and effector mechanisms that regulate sleep duration in mammals remain unclear. Here, we characterize a major signalling pathway for the transcriptional regulation of sleep in mice using adeno-associated virus-mediated somatic genetics analysis(4). Chimeric knockout of LKB1 kinase-an activator of AMPK-related protein kinase SIK3(5-7)-in adult mouse brain markedly reduces the amount and delta power-a measure of sleep depth-of non-rapid eye movement sleep (NREMS). Downstream of the LKB1-SIK3 pathway, gain or loss-of-function of the histone deacetylases HDAC4 and HDAC5 in adult brain neurons causes bidirectional changes of NREMS amount and delta power. Moreover, phosphorylation of HDAC4 and HDAC5 is associated with increased sleep need, and HDAC4 specifically regulates NREMS amount in posterior hypothalamus. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signalling pathways targeting transcription modulators to regulate daily sleep amount and demonstrate the power of somatic genetics in mouse sleep research."

基金机构："National Major Project of China Science and Technology Innovation for Brain Science and Brain-Inspired Technology [2021ZD0203400, Z181100001318004]; Beijing Municipal Commission of Science and Technology Commission and Chinese Ministry of Science and Technology"

基金资助正文："We thank M. Luo and F. Shao for sharing reagents; Y. Zhou, M. Zhao, Z. Li, W. Min, Y. Zhuang, Y. Sun, H. Huang, J. Wang and Y. Yin for technical assistance; and X. Wang, F. Shao, T. Chen, T. Han and M. Xu for discussion and comments on the manuscript. This work was supported by the National Major Project of China Science and Technology Innovation 2030 for Brain Science and Brain-Inspired Technology (2021ZD0203400 to Q.Liu), the innovation grant (Z181100001318004 to Q.Liu), and institution grants from the Beijing Municipal Commission of Science and Technology Commission and Chinese Ministry of Science and Technology."