Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip.

ABSTRACT: Bone loss caused by mechanical unloading is a threat to prolonged space flight and human health. Epigenetic modifications play a crucial role in varied biological processes, but the mechanism of histone modification on unloading-induced bone loss has rarely been studied. Here, we discovered for the first time that the methyltransferase Setdb1 was downregulated under the mechanical unloading both in vitro and in vivo so as to attenuate osteoblast proliferation. Furthermore, we found these interesting processes depended on the repression of Macrod2 expression triggered by Setdb1 catalyzing the formation of H3K9me3 in the promoter region. Mechanically, we revealed that Macrod2 was upregulated under mechanical unloading and suppressed osteoblast proliferation through the GSK-3β/β-catenin signa

SUBMITTER: Zhang L 

PROVIDER: S-EPMC9406310 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature