State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China.
Biochim Biophys Acta Gene Regul Mech. 2018 Feb;1861(2):106-116. doi: 10.1016/j.bbagrm.2017.12.009. Epub 2018 Jan 31.
The histone demethylase Jmjd3 plays a critical role in cell lineage specification and differentiation at various stages of development. However, its function during normal myeloid development remains poorly understood. Here, we carried out a systematic in vivo screen of epigenetic factors for their function in hematopoiesis and identified Jmjd3 as a new epigenetic factor that regulates myelopoiesis in zebrafish. We demonstrated that jmjd3 was essential for zebrafish primitive and definitive myelopoiesis, knockdown of jmjd3 suppressed the myeloid commitment and enhanced the erythroid commitment. Only overexpression of spi1 but not the other myeloid regulators rescued the myeloid development in jmjd3 morphants. Furthermore, preliminary mechanistic studies demonstrated that Jmjd3 could directly bind to the spi1 regulatory region to alleviate the repressive H3K27me3 modification and activate spi1 expression. Thus, our studies highlight that Jmjd3 is indispensable for early zebrafish myeloid development by promoting spi1 expression.
组蛋白去甲基化酶 Jmjd3 在细胞谱系特化和分化的各个发育阶段发挥着关键作用。然而，其在正常骨髓发育过程中的功能仍知之甚少。在这里，我们对表观遗传因子进行了系统的体内筛选，以研究它们在造血中的功能，并鉴定出 Jmjd3 是一种新的表观遗传因子，可调节斑马鱼中的髓系发育。我们证明 Jmjd3 对斑马鱼原始和确定的髓系发育是必不可少的，jmjd3 的敲低抑制了髓系的定向，并增强了红细胞的定向。只有 spi1 的过表达而不是其他髓系调节因子可以挽救 jmjd3 形态发生体中的髓系发育。此外，初步的机制研究表明，Jmjd3 可以直接结合 spi1 的调节区域，减轻抑制性 H3K27me3 修饰，并激活 spi1 的表达。因此，我们的研究强调，Jmjd3 通过促进 spi1 的表达对早期斑马鱼髓系发育是不可或缺的。
