Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response
AuthorGan, L; Sun, J; Yang, S; Zhang, X; Chen, W; Sun, Y; Wu, X; Cheng, C; Yuan, J; Li, A; ...
Source TitleCell Reports
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsGan, L., Sun, J., Yang, S., Zhang, X., Chen, W., Sun, Y., Wu, X., Cheng, C., Yuan, J., Li, A., Corbett, M. A., Dixon, M. P., Thomas, T., Voss, A. K., Gecz, J., Wang, G. -Z., Bonni, A., Li, Q. & Huang, J. (2020). Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. CELL REPORTS, 30 (11), pp.3717-+. https://doi.org/10.1016/j.celrep.2020.02.085.
Access StatusOpen Access
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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