TY  - JOUR
AU  - Gan, L
AU  - Sun, J
AU  - Yang, S
AU  - Zhang, X
AU  - Chen, W
AU  - Sun, Y
AU  - Wu, X
AU  - Cheng, C
AU  - Yuan, J
AU  - Li, A
AU  - Corbett, MA
AU  - Dixon, MP
AU  - Thomas, T
AU  - Voss, AK
AU  - Gecz, J
AU  - Wang, G-Z
AU  - Bonni, A
AU  - Li, Q
AU  - Huang, J
Y2  - 2020/11/27
Y1  - 2020/03/17
SN  - 2211-1247
UR  - http://hdl.handle.net/11343/252360
AB  - 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.
LA  - English
PB  - CELL PRESS
T1  - Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response
DO  - 10.1016/j.celrep.2020.02.085
IS  - Cell Reports
VL  - 30
IS  - 11
SP  - 3717-+
L1  - /bitstream/handle/11343/252360/PIIS221112472030259X.pdf?sequence=1&isAllowed=y
ER  -