Restoration of H3k27me3 Modification Epigenetically Silences Cry1 Expression and Sensitizes Leptin Signaling to Reduce Obesity-Related Properties.

ABSTRACT: 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, en

SUBMITTER: Wei Y 

PROVIDER: S-EPMC8292908 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature