Correlation Engine 2.0
Clear Search sequence regions


  • chromatin (1)
  • Cry1 (6)
  • drug target (1)
  • homeostasis (1)
  • human (1)
  • hypothalamus (2)
  • Kdm6a (8)
  • leptin (7)
  • Lys4 (1)
  • mice (3)
  • obesity mice (2)
  • Seq (1)
  • signal (1)
  • weight (2)
  • weight increases (1)
  • Sizes of these terms reflect their relevance to your search.

    The trimethylation on histone H3 lysine 27 (H3k27me3), a transcriptionally repressive epigenetic mark of permissive chromatin, can be removed by the histone lysine demethylase 6a (Kdm6a). However, the physiological function of H3k27me3 and Kdm6a on circadian genes remains largely elusive. With the ChIP-Seq and mRNA microarray assays, a critical role is identified for Kdm6a in the regulation of H3k27me3 to impact the expression of Crytochrome 1 (Cry1) in the hypothalamus of diet induced obesity mice. More importantly, both conditional knockout and pharmacological inhibition of Kdm6a reduce body weight and stabilize blood glucose homeostasis. Although a Kdm6a inhibitor fails to decrease body weight in leptin receptor-deficient db/db mice, it significantly decreases Cry1 expression, enhances sensitivity to exogenous leptin administration, and blocks body weight increases in endo-leptin-deficient ob/ob mice. Moreover, gene analysis of the human hypothalamus further reveals a positive correlation between Kdm6a and Cry1. The results show that inhibition of Kdm6a reduces the Cry1 expression and sensitizes leptin signaling to combat obesity-related disease. Therefore, it implicates Kdm6a as an attractive drug target for obesity and metabolic disorders. © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.

    Citation

    Yan Wei, Jun Chen, Xing Xu, Fan Li, Kun Wu, Yingying Jiang, Yuqing Rao, Chen Zhao, Wantao Chen, Xu Wang. Restoration of H3k27me3 Modification Epigenetically Silences Cry1 Expression and Sensitizes Leptin Signaling to Reduce Obesity-Related Properties. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021 Jul;8(14):2004319

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 34306972

    View Full Text