Chromatin-binding protein PHF6 regulates activity-dependent transcriptional networks to promote hunger response

Gan, L; Sun, J; Yang, S; Zhang, X; Chen, W; Sun, Y; Wu, X; Cheng, C; Yuan, J; Li, A; Corbett, MA; Dixon, MP; Thomas, T; Voss, AK; Gecz, J; Wang, GZ; Bonni, A; Li, Q; Huang, J

Author(s): Gan, L; Sun, J; Yang, S; Zhang, X; Chen, W; Sun, Y; Wu, X; Cheng, C; Yuan, J; Li, A; Corbett, MA; Dixon, MP; Thomas, T; Voss, AK; Gecz, J; Wang, GZ; Bonni, A; Li, Q; Huang, J;
Details: Publication Year 2020-03-17,Volume 30,Issue #11,Page 3717-3728e6
Journal Title: Cell Reports
Publication Type: Journal Article
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.
Publisher: Cell Press
Research Division(s): Epigenetics And Development
PubMed ID: 32187544
Publisher's Version: https://doi.org/10.1016/j.celrep.2020.02.085
Open Access at Publisher's Site: https://doi.org/10.1016/j.celrep.2020.02.085
NHMRC Grants: NHMRC/1029481, NHMRC/1084248, NHMRC/1003435, NHMRC/575512, NHMRC/1081421,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-03-24 01:39:41

Last Modified: 2020-03-24 02:03:14