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Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response.
Gan, Linhua; Sun, Jingjing; Yang, Shuo; Zhang, Xiaocui; Chen, Wu; Sun, Yiyu; Wu, Xiaohua; Cheng, Cheng; Yuan, Jing; Li, Anan; Corbett, Mark A; Dixon, Mathew P; Thomas, Tim; Voss, Anne K; Gécz, Jozef; Wang, Guang-Zhong; Bonni, Azad; Li, Qian; Huang, Ju.
Affiliation
  • Gan L; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Sun J; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Yang S; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Zhang X; Core Facility of Basic Medical Sciences, Basic Medicine Faculty of Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Chen W; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
  • Sun Y; Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China.
  • Wu X; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Cheng C; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Yuan J; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China; HUST-Suzhou Institute for Brainmatics, Suzhou 215125, China.
  • Li A; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China; HUST-Suzhou Institute for Brainmatics, Suzhou 215125, China.
  • Corbett MA; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
  • Dixon MP; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
  • Thomas T; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, VIC, Australia.
  • Voss AK; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, VIC, Australia.
  • Gécz J; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
  • Wang GZ; CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.
  • Bonni A; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Li Q; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai 201210, China. Electronic address: liqian@shsmu.edu.
  • Huang J; Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai 201210, China. Electronic address: juhuang@shsmu.edu
Cell Rep ; 30(11): 3717-3728.e6, 2020 03 17.
Article in En | MEDLINE | ID: mdl-32187544
Understanding the mechanisms of activity-dependent gene transcription underlying adaptive behaviors is challenging at neuronal-subtype resolution. Using cell-type specific molecular analysis in agouti-related peptide (AgRP) neurons, we reveal that the profound hunger-induced transcriptional changes greatly depend on plant homeodomain finger protein 6 (PHF6), a transcriptional repressor enriched in AgRP neurons. Loss of PHF6 in the satiated mice results in a hunger-state-shifting transcriptional profile, while hunger fails to further induce a rapid and robust activity-dependent gene transcription in PHF6-deficient AgRP neurons. We reveal that PHF6 binds to the promoters of a subset of immediate-early genes (IEGs) and that this chromatin binding is dynamically regulated by hunger state. Depletion of PHF6 decreases hunger-driven feeding motivation and makes the mice resistant to body weight gain under repetitive fasting-refeeding conditions. Our work identifies a neuronal subtype-specific transcriptional repressor that modulates transcriptional profiles in different nutritional states and enables adaptive eating behavior.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins / Chromatin / Hunger / Gene Regulatory Networks / Neurons Type of study: Prognostic_studies Aspects: Determinantes_sociais_saude Limits: Animals Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins / Chromatin / Hunger / Gene Regulatory Networks / Neurons Type of study: Prognostic_studies Aspects: Determinantes_sociais_saude Limits: Animals Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country: Country of publication: