College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Cell Rep. 2018 Apr 10;23(2):389-403. doi: 10.1016/j.celrep.2018.03.051.
The arginine methylation status of histones dynamically changes during many cellular processes, including hematopoietic stem/progenitor cell (HSPC) development. The arginine methyltransferases and the readers that transduce the histone codes have been defined. However, whether arginine demethylation actively occurs in cells and what enzyme demethylates the methylarginine residues during various cellular processes are unknown. We report that JMJD1B, previously identified as a lysine demethylase for H3K9me2, mediates arginine demethylation of H4R3me2s and its intermediate, H4R3me1. We show that demethylation of H4R3me2s and H3K9me2s in promoter regions is correlated with active gene expression. Furthermore, knockout of JMJD1B blocks demethylation of H4R3me2s and/or H3K9me2 at distinct clusters of genes and impairs the activation of genes important for HSPC differentiation and development. Consequently, JMJD1B mice show defects in hematopoiesis. Altogether, our study demonstrates that demethylase-mediated active arginine demethylation process exists in eukaryotes and that JMJD1B demethylates both H4R3me2s and H3K9me2 for epigenetic programming during hematopoiesis.
组蛋白的精氨酸甲基化状态在许多细胞过程中动态变化，包括造血干细胞/祖细胞（HSPC）的发育。已经定义了精氨酸甲基转移酶和转导组蛋白密码的读取器。然而，细胞中是否会主动发生精氨酸去甲基化，以及在各种细胞过程中哪种酶会使甲基精氨酸残基去甲基化，目前尚不清楚。我们报告说，先前被鉴定为 H3K9me2 赖氨酸去甲基酶的 JMJD1B 介导 H4R3me2s 和其中间产物 H4R3me1 的精氨酸去甲基化。我们表明，启动子区域中 H4R3me2s 和 H3K9me2 的去甲基化与活性基因表达相关。此外，JMJD1B 的敲除会阻止特定基因簇中 H4R3me2s 和/或 H3K9me2 的去甲基化，并损害 HSPC 分化和发育过程中重要基因的激活。因此，JMJD1B 小鼠表现出造血缺陷。总的来说，我们的研究表明，在真核生物中存在酶介导的活性精氨酸去甲基化过程，并且 JMJD1B 为造血过程中的表观遗传编程去甲基化 H4R3me2s 和 H3K9me2。
