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Updated: May 15, 2025

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Histone chaperone HIRA facilitates transcription elongation to regulate insulin sensitivity and obesity-associated
Danyang Wan1, Ji-Eun Lee1, Young-Kwon Park1
1Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Adipose tissue is essential for maintaining glucose and lipid homeostasis in mammals. The histone chaperone HIRA has been reported to play a lineage- and stage-selective role during development. However, its role in adipose tissue development and function as well as its working mechanism remain unknown. Here we show that tissue-specific knockout of histone chaperone HIRA in mice impairs insulin sensitivity and alleviates adipose tissue expansion during high-fat diet-induced obesity, but only moderately affects embryonic development of adipose tissue. Mechanistically, HIRA is selectively required for expression of genes critical for insulin response and lipogenesis, rather than adipogenesis, in adipose tissue. By acute depletion of HIRA protein and by mapping HIRA genomic localization in adipocytes, we demonstrate that HIRA binds to promoters and enhancers of insulin response and lipogenesis genes and regulates their expression by facilitating transcription elongation. Our findings not only identify HIRA as an epigenomic regulator of insulin sensitivity, lipogenesis, and obesity-associated adipose expansion, but also reveal a novel mechanism by which HIRA regulates transcription.
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