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Type: Journal article
Title: Chromatin-binding protein PHF6 regulates activity-dependent transcriptional networks to promote hunger response
Author: Gan, 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.
Gécz, J.
Wang, G.-Z.
Bonni, A.
Li, Q.
Huang, J.
Citation: Cell Reports, 2020; 30(11):3717-3728.e6
Publisher: Elsevier
Issue Date: 2020
ISSN: 2211-1247
Statement of
Linhua Gan, Jingjing Sun, Shuo Yang, Xiaocui Zhang ... Mark A. Corbett ... Jozef Gécz ... et al.
Abstract: 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.
Keywords: AgRP neuron
Börjeson-Forssman-Lehmann syndrome
activity-dependent gene transcription
hunger-driven feeding behavior
immediate-early genes
Rights: © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
DOI: 10.1016/j.celrep.2020.02.085
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