Dataset Information

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

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.

SUBMITTER: Yan L

PROVIDER: S-EPMC8373154 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Yan Linyu L Jin Weiwei W Zhao Qingwen Q Cui Xuan X Shi Ting T Xu Yingjiang Y Li Feiyan F Jin Wenfang W Zhang Zhe Z Zhang Zhao Z Tang Qi-Qun QQ Pan Dongning D

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20210627 16

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 suppre ...[more]

PMID: 34180153

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Project description:BackgroundInflammatory response after myocardial infarction (MI) is essential for cardiac healing, whereas excessive and prolonged inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanistic insight of these tightly controlled inflammatory processes has a significant impact on post-MI recovery and therapy. Here, we uncover the critical role of small GTPase RhoE in post-MI recovery and its clinical implication.MethodsThree genetic mouse lines are used: global RhoE knockout, cardiomyocyte-specific RhoE heterozygous, and cardiomyocyte-specific RhoE overexpression mice. A set of molecular signaling experiments, including bimolecular fluorescence complementation, immunoprecipitation, electrophoretic mobility shift assay, and mRNA microarray analysis, were conducted. Permanent ligation of the left anterior descending artery was performed, followed by the assessments of cardiac function, inflammation, and survival in the first week after MI. Finally, we examined the correlation of the expression levels of RhoE in MI patient heart and patient prognosis.ResultsRhoE deficiency turns on a group of proinflammatory gene expressions in mouse heart. Mice with cardiomyocyte-specific haploinsufficiency exhibit excessive inflammatory response with deleterious cardiac function after MI. A profound increase in nuclear factor-κB activity is detected in the mutant heart and the isolated cardiomyocytes. We further find that the expression of RhoE is upregulated in response to MI. Mechanistically, RhoE interacts with p65 and p50 individually in cytosol and blocks their nuclear translocation. RhoE also occupies the dimerization domain of p65 and subsequently disrupts the heterodimerization between p65 and p50. Cardiac RhoE overexpression inhibits nuclear factor-κB activity, restrains post-MI inflammation, and improves cardiac function and survival. Consistently, we find that the expression level of RhoE is elevated in the heart of patients with MI and that the patients with a higher expression level of RhoE exhibit a better prognosis in cardiac function recovery.ConclusionsThe study uncovers RhoE as a new fine-tuning factor modulating MI-induced inflammation and promoting injured heart recovery. RhoE may serve as a new potential biomarker for the assessment of MI patient prognosis. Manipulation of RhoE could be as a potential therapeutic approach for MI and other inflammatory diseases.

Dataset Information

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

Publications

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

Similar Datasets

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