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

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    Author
    Gan, L; Sun, J; Yang, S; Zhang, X; Chen, W; Sun, Y; Wu, X; Cheng, C; Yuan, J; Li, A; ...
    Date
    2020-03-17
    Source Title
    Cell Reports
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Voss, Anne
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
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    Document Type
    Journal Article
    Citations
    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., 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 Status
    Open Access
    URI
    http://hdl.handle.net/11343/252360
    DOI
    10.1016/j.celrep.2020.02.085
    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.

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