State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):286-290. doi: 10.1016/j.bbrc.2018.11.023. Epub 2018 Nov 15.
Glucose homeostasis is a key event during many physiological and pathological processes. Histone modifications have emerged as vital factors influencing this process. DPY30, a core subunit of SET1/MLL family histone H3K4 methyltransferase complexes, has been reported to be amplified in cancers. However, the role of DPY30 in glucose homeostasis remains unclear. Here we reported that DPY30 regulated H3K4me3 recruitment to control the expression of Hif1α and its targeted glycolytic genes. Specifically, DPY30 promoted H3K9Ac recruitment via inhibiting SIRT6 occupancy on these gene promoters. Finally, we observed significant upregulation of DPY30 mRNA expression in hepatocellular carcinoma samples from datasets. Taken together, our results reveal a critical role of DPY30 in glucose homeostasis and might offer new therapeutic and diagnostic opportunities for cancers.
葡萄糖稳态是许多生理和病理过程中的关键事件。组蛋白修饰已成为影响这一过程的重要因素。DPY30 是 SET1/MLL 家族组蛋白 H3K4 甲基转移酶复合物的核心亚基，已被报道在癌症中扩增。然而，DPY30 在葡萄糖稳态中的作用尚不清楚。在这里，我们报道 DPY30 调节 H3K4me3 的募集以控制 Hif1α 的表达及其靶向糖酵解基因。具体来说，DPY30 通过抑制 SIRT6 在这些基因启动子上的占据来促进 H3K9Ac 的募集。最后，我们在数据集的肝细胞癌样本中观察到 DPY30 mRNA 表达的显著上调。总之，我们的研究结果揭示了 DPY30 在葡萄糖稳态中的关键作用，并为癌症提供了新的治疗和诊断机会。
