Abstract

Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.

The regulatory networks that govern chromatin accessibility and gene expression in brown and beigeadipocytes remain to be fully elucidated. Here the authors use fat-specific inactivation of BAF60a toreveal a differential role for this chromatin remodeling factor in brown fat thermogenesis and coldinduced browning of inguinal fat.

Details

Title
BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning
Author
Liu Tongyu 1 ; Lin, Mi 2 ; Xiong Jing 2 ; Orchard, Peter 3 ; Yu, Qi 2 ; Yu, Lei 2 ; Xu-Yun, Zhao 2 ; Zhuo-Xian, Meng 4 ; Parker Stephen C J 3 ; Lin, Jiandie D 2   VIAFID ORCID Logo  ; Li, Siming 2 

1  University of Michigan, Life Sciences Institute and Department of Cell and Developmental Biology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
2  University of Michigan, Life Sciences Institute and Department of Cell and Developmental Biology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
3  University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Human Genetics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
4  Key Laboratory of Disease Proteomics of Zhejiang Province, Department of Pathology and Pathophysiology, Hangzhou, China (GRID:grid.214458.e); Zhejiang University, Chronic Disease Research Institute of School of Public Health, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-16148-1
ProQuest document ID
2402386637
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.