CCAAT/增强子结合蛋白α的类泛素化修饰通过调控斑马鱼中的runx1参与造血干/祖细胞发育。
Sumoylation of CCAAT/enhancer-binding protein α is implicated in hematopoietic stem/progenitor cell development through regulating runx1 in zebrafish.
作者信息
Yuan Hao, Zhang Tao, Liu Xiaohui, Deng Min, Zhang Wenqing, Wen Zilong, Chen Saijuan, Chen Zhu, de The Hugues, Zhou Jun, Zhu Jun
机构信息
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, Shanghai, China.
出版信息
Sci Rep. 2015 Mar 11;5:9011. doi: 10.1038/srep09011.
The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.
小泛素相关修饰物（SUMO）参与多种细胞过程，包括基因组完整性的维持、核运输、转录和信号转导。然而，SUMO化在造血过程中的生物学功能尚未得到充分探索。我们在此表明，在SUMO缺陷的斑马鱼胚胎中，定型造血干细胞/祖细胞（HSPCs）会减少。SUMO化的受损会减弱HSPC的生成和增殖。低SUMO化引发的HSPC缺陷是CCAAT/增强子结合蛋白α（C/ebpα）依赖性的。至关重要的是，SUMO-C/ebpα融合蛋白至少部分通过恢复runx1表达来挽救SUMO缺陷胚胎中的造血缺陷。虽然C/ebpα依赖性转录参与髓系分化，但我们在此的研究表明，C/ebpα SUMO化对于定型造血过程中HSPC的发育至关重要。
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