JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells
Sihui Li,
Shafat Ali,
Xiaotao Duan,
Songbai Liu,
Juan Du,
Changwei Liu,
Huifang Dai,
Mian Zhou,
Lina Zhou,
Lu Yang,
Peiguo Chu,
Ling Li,
Ravi Bhatia,
Dustin E. Schones,
Xiwei Wu,
Hong Xu,
Yuejin Hua,
Zhigang Guo,
Yanzhong Yang,
Li Zheng,
Binghui Shen
Affiliations
Sihui Li
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Shafat Ali
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Xiaotao Duan
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Songbai Liu
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Juan Du
Department of Diabetes Complications & Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA; Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA
Changwei Liu
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Huifang Dai
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Mian Zhou
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Lina Zhou
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Lu Yang
Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA
Peiguo Chu
Department of Pathology, Beckman Research Institute, City of Hope, Duarte, CA, USA
Ling Li
Department of Hematologic Malignancy Translational Science, Beckman Research Institute, City of Hope, Duarte, CA, USA
Ravi Bhatia
Department of Hematologic Malignancy Translational Science, Beckman Research Institute, City of Hope, Duarte, CA, USA
Dustin E. Schones
Department of Diabetes Complications & Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA
Xiwei Wu
Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA
Hong Xu
Colleges of Life Sciences and Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China
Yuejin Hua
Colleges of Life Sciences and Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China
Zhigang Guo
College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China
Yanzhong Yang
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA
Li Zheng
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA; Corresponding author
Binghui Shen
Departments of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA; Corresponding author
Summary: 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. : Li et al. identify the arginine demethylase (RDM) activity of JMJD1B, a known lysine demethylase (KDM). They reveal that JMJD1B actively mediates demethylation of histone markers H4R3me2s and H3K9me2 in hematopoietic stem/progenitor cells (HSPCs). Keywords: JMJD1B, KDM3B, PRMT5, arginine demethylase, histone, epigenetic programming, gene expression, hematopoiesis
