PWWP2B Fine‐Tunes Adipose Thermogenesis by Stabilizing HDACs in a NuRD Subcomplex

• Main Authors: Linyu Yan, Weiwei Jin, Qingwen Zhao, Xuan Cui, Ting Shi, Yingjiang Xu, Feiyan Li, Wenfang Jin, Zhe Zhang, Zhao Zhang, Qi‐Qun Tang, Dongning Pan
• Format: Article
• Language: English
• Published: Wiley 2021-08-01
• Series: Advanced Science
• Subjects: adipocyte thermogenesis; histone deacetylation; PWWP2B; the NuRD complex
• Online Access: https://doi.org/10.1002/advs.202102060

Abstract Histone deacetylases (HDACs) are widely involved in many biological processes, as well as in control of brown and beige adipose physiology, but the precise molecular mechanisms by which HDACs are assembled into transcriptional machinery to fine‐tune thermogenic program remain ill‐defined. PWWP domain containing 2b (PWWP2B), which is identified as a component of the nucleosome remodeling and deacetylation complex (NuRD), interacts and stabilizes HDAC1/2 at the thermogenic gene promoters to suppress their expression. Ablation of Pwwp2b promotes adipocyte thermogenesis and ameliorates diet‐induced obesity in vivo. Intriguingly, Pwwp2b is not only a brown fat‐enriched gene but also dramatically induced by cold and sympathetic stimulation, which may serve as a physiological brake to avoid over‐activation of thermogenesis in brown and beige fat cells.