Details

Autor(en) / Beteiligte

• Zhao, Qingwen
• Zhang, Zhe
• Rong, Weiqiong
• Jin, Weiwei
• Yan, Linyu
• Jin, Wenfang
• Xu, Yingjiang
• Cui, Xuan
• Tang, Qi-Qun
• Pan, Dongning

Titel

KMT5c modulates adipocyte thermogenesis by regulating Trp53 expression

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2020-09, Vol.117 (36), p.22413-22422

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Brown and beige adipocytes harbor the thermogenic capacity to adapt to environmental thermal or nutritional changes. Histone methylation is an essential epigenetic modification involved in the modulation of nonshivering thermogenesis in adipocytes. Here, we describe a molecular network leading by KMT5c, a H4K20 methyltransferase, that regulates adipocyte thermogenesis and systemic energy expenditure. The expression of Kmt5c is dramatically induced by a β3-adrenergic signaling cascade in both brown and beige fat cells. Depleting Kmt5c in adipocytes in vivo leads to a decreased expression of thermogenic genes in both brown and subcutaneous (s.c.) fat tissues. These mice are prone to high-fat-diet-induced obesity and develop glucose intolerance. Enhanced transformation related protein 53 (Trp53) expression in Kmt5c knockout (KO) mice, that is due to the decreased repressive mark H4K20me3 on its proximal promoter, is responsible for the metabolic phenotypes. Together, these findings reveal the physiological role for KMT5c-mediated H4K20 methylation in the maintenance and activation of the thermogenic program in adipocytes.