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  • Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response.

Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response.

Cell reports (2020-03-19)
Linhua Gan, Jingjing Sun, Shuo Yang, Xiaocui Zhang, Wu Chen, Yiyu Sun, Xiaohua Wu, Cheng Cheng, Jing Yuan, Anan Li, Mark A Corbett, Mathew P Dixon, Tim Thomas, Anne K Voss, Jozef Gécz, Guang-Zhong Wang, Azad Bonni, Qian Li, Ju Huang
摘要

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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Sigma-Aldrich
抗-PHF6 兔抗, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
SC144 hydrochloride, ≥98% (HPLC)