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

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 Gecz; Guang Zhong Wang; Azad Bonni; Qian Li; Ju Huang

doi:10.1016/j.celrep.2020.02.085

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

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 Gecz, Guang Zhong Wang, Azad Bonni, Qian Li, Ju Huang

Childhood Disability Prevention

Research output: Contribution to 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.

Language	English
Pages	3717-3728.e6
Journal	Cell Reports
Volume	30
Issue number	11
DOIs	10.1016/j.celrep.2020.02.085
Publication status	Published - 17 Mar 2020

Keywords

AgRP neuron
BFLS
Börjeson-Forssman-Lehmann syndrome
IEGs
PHF6
activity-dependent gene transcription
hunger-driven feeding behavior
immediate-early genes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gan, L., Sun, J., Yang, S., Zhang, X., Chen, W., Sun, Y., ... Huang, J. (2020). Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. Cell Reports, 30(11), 3717-3728.e6. https://doi.org/10.1016/j.celrep.2020.02.085

Gan, Linhua ; Sun, Jingjing ; Yang, Shuo ; Zhang, Xiaocui ; Chen, Wu ; Sun, Yiyu ; Wu, Xiaohua ; Cheng, Cheng ; Yuan, Jing ; Li, Anan ; Corbett, Mark A. ; Dixon, Mathew P. ; Thomas, Tim ; Voss, Anne K. ; Gecz, Jozef ; Wang, Guang Zhong ; Bonni, Azad ; Li, Qian ; Huang, Ju. / Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. In: Cell Reports. 2020 ; Vol. 30, No. 11. pp. 3717-3728.e6.

@article{2a6f68a80b5949a49d720d9d05ff43f8,

title = "Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response",

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, BFLS, B{\"o}rjeson-Forssman-Lehmann syndrome, IEGs, PHF6, activity-dependent gene transcription, hunger-driven feeding behavior, immediate-early genes",

author = "Linhua Gan and Jingjing Sun and Shuo Yang and Xiaocui Zhang and Wu Chen and Yiyu Sun and Xiaohua Wu and Cheng Cheng and Jing Yuan and Anan Li and Corbett, {Mark A.} and Dixon, {Mathew P.} and Tim Thomas and Voss, {Anne K.} and Jozef Gecz and Wang, {Guang Zhong} and Azad Bonni and Qian Li and Ju Huang",

year = "2020",

month = "3",

day = "17",

doi = "10.1016/j.celrep.2020.02.085",

language = "English",

volume = "30",

pages = "3717--3728.e6",

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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 2020, 'Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response', Cell Reports, vol. 30, no. 11, pp. 3717-3728.e6. https://doi.org/10.1016/j.celrep.2020.02.085

Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. / Gan, Linhua; Sun, Jingjing; Yang, Shuo; Zhang, Xiaocui; Chen, Wu; Sun, Yiyu; Wu, Xiaohua; Cheng, Cheng; Yuan, Jing; Li, Anan; Corbett, Mark A.; Dixon, Mathew P.; Thomas, Tim; Voss, Anne K.; Gecz, Jozef; Wang, Guang Zhong; Bonni, Azad; Li, Qian; Huang, Ju.

In: Cell Reports, Vol. 30, No. 11, 17.03.2020, p. 3717-3728.e6.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response

AU - Gan, Linhua

AU - Sun, Jingjing

AU - Yang, Shuo

AU - Zhang, Xiaocui

AU - Chen, Wu

AU - Sun, Yiyu

AU - Wu, Xiaohua

AU - Cheng, Cheng

AU - Yuan, Jing

AU - Li, Anan

AU - Corbett, Mark A.

AU - Dixon, Mathew P.

AU - Thomas, Tim

AU - Voss, Anne K.

AU - Gecz, Jozef

AU - Wang, Guang Zhong

AU - Bonni, Azad

AU - Li, Qian

AU - Huang, Ju

PY - 2020/3/17

Y1 - 2020/3/17

N2 - 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.

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.

KW - AgRP neuron

KW - BFLS

KW - Börjeson-Forssman-Lehmann syndrome

KW - IEGs

KW - PHF6

KW - activity-dependent gene transcription

KW - hunger-driven feeding behavior

KW - immediate-early genes

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U2 - 10.1016/j.celrep.2020.02.085

DO - 10.1016/j.celrep.2020.02.085

M3 - Article

VL - 30

SP - 3717-3728.e6

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

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Access to Document

10.1016/j.celrep.2020.02.085

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