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HMGB2 orchestrates mitotic clonal expansion by binding to the promoter of C/EBPβ to facilitate adipogenesis
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HMGB2 orchestrates mitotic clonal expansion by binding to the promoter of C/EBPβ to facilitate adipogenesis
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Journal Article
HMGB2 orchestrates mitotic clonal expansion by binding to the promoter of C/EBPβ to facilitate adipogenesis
2021
Overview
High-mobility group box 2 (HMGB2) is an abundant, chromatin-associated protein that plays an essential role in the regulation of transcription, cell proliferation, differentiation, and tumorigenesis. However, the underlying mechanism of HMGB2 in adipogenesis remains poorly known. Here, we provide evidence that HMGB2 deficiency in preadipocytes impedes adipogenesis, while overexpression of HMGB2 increases the potential for adipogenic differentiation. Besides, depletion of HMGB2 in vivo caused the decrease in body weight, white adipose tissue (WAT) mass, and adipocyte size. Consistently, the stromal vascular fraction (SVF) of adipose tissue derived from
hmgb2
−/−
mice presented impaired adipogenesis. When
hmgb2
−/−
mice were fed with high-fat diet (HFD), the body size, and WAT mass were increased, but at a lower rate. Mechanistically, HMGB2 mediates adipogenesis via enhancing expression of C/EBPβ by binding to its promoter at “GGGTCTCAC” specifically during mitotic clonal expansion (MCE) stage, and exogenous expression of C/EBPβ can rescue adipogenic abilities of preadipocytes in response to HMGB2 inhibition. In general, our findings provide a novel mechanism of HMGB2-C/EBPβ axis in adipogenesis and a potential therapeutic target for obesity.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/1
/ 13/89
/ 38/77
/ 64
/ 64/60
/ 82
/ 96
/ Ablation
/ Adipocytes, White - metabolism
/ Adipocytes, White - pathology
/ Adipose Tissue, White - metabolism
/ Adipose Tissue, White - pathology
/ Animals
/ Biomedical and Life Sciences
/ Body fat
/ CCAAT-Enhancer-Binding Protein-beta - genetics
/ CCAAT-Enhancer-Binding Protein-beta - metabolism
/ Female
/ Lipids
/ Male
/ Mice
/ Mitosis
/ Obesity
/ Proteins
