西亚试剂：β-Arrestin1 Regulates Zebrafish Hematopoiesis through Bindi

β-Arrestin1 Regulates Zebrafish Hematopoiesis through Binding to YY1 and Relieving Polycomb Group Repression

Rui Yue1, Jiuhong Kang1, 2, Cong Zhao1, Wenxiang Hu1, Yawei Tang1, Xiaosong Liu1 and Gang Pei1, 2, ,

1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences; Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
2 School of Life Science and Technology, Tongji University, 200092, Shanghai, China

β-Arrestin1 is a multifunctional protein critically involved in signal transduction. Recently, it is also identified as a nuclear transcriptional regulator, but the underlying mechanisms and physiological significance remain to be explored. Here, we identified β-arrestin1 as an evolutionarily conserved protein essential for zebrafish development. Zebrafish embryos depleted of β-arrestin1 displayed severe posterior defects and especially failed to undergo hematopoiesis. In addition, the expression of cdx4, a critical regulator of embryonic blood formation, and its downstream hox genes were downregulated by depletion of β-arrestin1, while injection of cdx4, hoxa9a or hoxb4a mRNA rescued the hematopoietic defects. Further mechanistic studies revealed that β-arrestin1 bound to and sequestered the polycomb group (PcG) recruiter YY1, and relieved PcG-mediated repression of cdx4-hox pathway, thus regulating hematopoietic lineage specification. Taken together, this study demonstrated a critical role of β-arrestin1 during zebrafish primitive hematopoiesis, as well as an important regulator of PcG proteins and cdx4-hox pathway.

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