ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes.


Journal

Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 26 06 2021
accepted: 07 09 2021
pubmed: 9 10 2021
medline: 5 4 2022
entrez: 8 10 2021
Statut: ppublish

Résumé

Energy-storing white adipocytes maintain their identity by suppressing the energy-burning thermogenic gene program of brown and beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional coregulator ZFP423 and brown fat determination factor EBF2 is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread "browning" of WAT in adult mice. Mechanistically, ZFP423 recruits the NuRD corepressor complex to EBF2-bound thermogenic gene enhancers. Loss of adipocyte

Identifiants

pubmed: 34620682
pii: gad.348780.121
doi: 10.1101/gad.348780.121
pmc: PMC8559675
doi:

Substances chimiques

Basic Helix-Loop-Helix Transcription Factors 0
DNA-Binding Proteins 0
Ebf2 protein, mouse 0
Ebfaz protein, mouse 0
PPAR gamma 0
Pparg protein, mouse 0
Transcription Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1461-1474

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK119163
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121801
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123356
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK104789
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK118620
Pays : United States

Informations de copyright

© 2021 Shao et al.; Published by Cold Spring Harbor Laboratory Press.

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Auteurs

Mengle Shao (M)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Qianbin Zhang (Q)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Ashley Truong (A)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Bo Shan (B)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Lavanya Vishvanath (L)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Lin Li (L)

Department of Pediatrics, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Department of Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Patrick Seale (P)

Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Rana K Gupta (RK)

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

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Classifications MeSH