The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression |
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| Authors: | Shan-He Yu Kang-Yong Zhu Fan Zhang Juan Wang Hao Yuan Yi Chen Yi Jin Mei Dong Lei Wang Xiao-E Jia Lei Gao Zhi-Wei Dong Chun-Guang Ren Li-Ting Chen Qiu-Hua Huang Min Deng Leonard I Zon Yi Zhou Ting-Xi Liu |
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| Institution: | 1. 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;2. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;3. Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China;4. Sino-French Research Center for Life Sciences and Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;5. Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;6. Harvard Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA;7. Stem Cell Program and Division of Hematology/Oncology, Boston Children''s Hospital, Pediatric Hematology/Oncology at Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA |
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| Abstract: | 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. |
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| Keywords: | Histone demethylase Myelopoiesis Zebrafish |
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