棕色脂肪细胞和米色脂肪细胞具有将化学能转变为热能散出体外的特性，因而它们能调节体温，并有助于增加机体能量消耗来预防和治疗肥胖。组蛋白乙酰化和甲基化修饰都参与调节棕色脂肪和米色脂肪功能。I型组蛋白去乙酰化酶（HDACs）抑制剂可以诱导棕色脂肪细胞线粒体合成，增强氧化代谢，促进白色脂肪棕色化。目前，组蛋白去乙酰化酶抑制剂成为治疗糖尿病患者胰岛素抵抗的潜在新药物。但是我们对I型HDACs在脂肪细胞中如何被召募到靶基因的启动子区还不了解。本研究发现Pwwp2b基因在棕色脂肪组织中表达水平较高，是产热基因表达的负性调节蛋白,可与I型HDACs相互作用。它可能是表观遗传修饰的Readers，利用其PWWP结构域识别并结合特异性甲基化修饰组蛋白，并召募HDACs到产热基因启动子区发挥去乙酰化作用，从而抑制产热基因表达。本研究将为探索以Pwwp2b作为药物靶点治疗肥胖等代谢性疾病奠定基础。

Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Histone acetylation as well as methylation plays an essential role in modulating thermogenic adipocytes gene program and metabolism. Class I HDAC inhibitors were shown to induce brown adipose tissue mitochondrial biogenesis, enhance oxidative metabolism and increase browning of white adipose tissue. HDAC inhibitors demonstrate an outstanding insulin sensitizing activity in various preclinical models and clinical trials and may be developed into future therapeutics for insulin resistance and type 2 diabetes. However, our understanding of how HDACs are recruited to the target gene promoters in adipocytes is limited. Here our initial data show Pwwp2b is a BAT-enriched gene and regulates expression of thermogenic genes negatively. Pwwp2b can interact with class I HDACs. We deduce that Pwwp2b binds to specific methylated histone through its PWWP domain and inhibits thermogenic gene program by recruiting class I HDACs to target gene promoters. Pwwp2b may work as an epigenetic reader to coordinate histone methylation and acetylation. Our study will pave the way of Pwwp2b toward possible molecular targets in therapeutics of obesity.