BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning.

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Tytuł:: BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning.
Autorzy:: Liu T; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Mi L; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Xiong J; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Orchard P; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Yu Q; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Yu L; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Zhao XY; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Meng ZX; Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.; Chronic Disease Research Institute of School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Parker SCJ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Lin JD; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA. .
Li S; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA. .
Źródło:: Nature communications [Nat Commun] 2020 May 13; Vol. 11 (1), pp. 2379. Date of Electronic Publication: 2020 May 13.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Cold Temperature*
Adipose Tissue, Brown/*metabolism
Adipose Tissue, White/*metabolism
Chromatin/*metabolism
Chromosomal Proteins, Non-Histone/*deficiency
Adipocytes, Brown/drug effects ; Adipocytes, Brown/metabolism ; Adipocytes, Brown/ultrastructure ; Adipose Tissue, Beige/metabolism ; Adipose Tissue, Brown/drug effects ; Adipose Tissue, White/drug effects ; Adrenocorticotropic Hormone/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Binding Sites/genetics ; Cells, Cultured ; Chromatin/genetics ; Chromosomal Proteins, Non-Histone/genetics ; Gene Expression/drug effects ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Thermogenesis/drug effects ; Thermogenesis/genetics
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Grant Information:: P30 DK020572 United States DK NIDDK NIH HHS; P30 DK089503 United States DK NIDDK NIH HHS; T32 HG000040 United States HG NHGRI NIH HHS
Substance Nomenclature:: 0 (Basic Helix-Loop-Helix Transcription Factors)
0 (Chromatin)
0 (Chromosomal Proteins, Non-Histone)
0 (Ebf2 protein, mouse)
0 (MRAP protein, mouse)
0 (Membrane Proteins)
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
0 (Smarcd1 protein, mouse)
9002-60-2 (Adrenocorticotropic Hormone)
Entry Date(s):: Date Created: 20200515 Date Completed: 20200810 Latest Revision: 20220422
Update Code:: 20240105
PubMed Central ID:: PMC7221096
DOI:: 10.1038/s41467-020-16148-1
PMID:: 32404872
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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.

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