Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, 050024, Hebei, China; No.1 Middle School of Yuxian, Yuxian, 075700, Hebei, China.
Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, 518036, Guangdong, China; Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
Int J Biochem Cell Biol. 2019 Apr;109:33-39. doi: 10.1016/j.biocel.2019.01.022. Epub 2019 Feb 1.
Erythropoietin (EPO) is a secreted hormone that stimulates the production of red blood cells, and the level of EPO is increased under hypoxia. The expression of EPO is regulated not only by the hypoxia-inducible factor (HIF) but also partly through epigenetic modifications, including histone acetylation and methylation. In this study, we report that histone H3K9 demethylase JMJD1 A is regulated by HIF-2α in HepG2 cells under hypoxia. Knockdown or over-expression of JMJD1 A can decrease or increase EPO expression, respectively. JMJD1 A can interact with HIF-2α to form a co-activator complex, which binds to the hypoxia response elements of EPO and increases EPO expression by catalyzing demethylation of H3K9me2, a transcription suppression marker. The results demonstrate that JMJD1 A is a co-activator of EPO expression.
促红细胞生成素（EPO）是一种分泌激素，可刺激红细胞生成，并且在缺氧下 EPO 水平增加。EPO 的表达不仅受缺氧诱导因子（HIF）调节，还部分通过表观遗传修饰（包括组蛋白乙酰化和甲基化）进行调节。在这项研究中，我们报告在缺氧条件下，HIF-2α 可调节 HepG2 细胞中的组蛋白 H3K9 去甲基酶 JMJD1A。JMJD1A 的敲低或过表达分别可降低或增加 EPO 的表达。JMJD1A 可与 HIF-2α 相互作用形成共激活因子复合物，该复合物与 EPO 的低氧反应元件结合，并通过催化 H3K9me2 的去甲基化（一种转录抑制标记物）来增加 EPO 的表达。结果表明，JMJD1A 是 EPO 表达的共激活因子。
