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. © 2009 Elsevier Inc. All rights reserved.
Yue, R., Kang, J., Zhao, C., Hu, W., Tang, Y., Liu, X., & Pei, G. (2009). β-Arrestin1 Regulates Zebrafish Hematopoiesis through Binding to YY1 and Relieving Polycomb Group Repression. Cell, 139(3), 535–546. https://doi.org/10.1016/j.cell.2009.08.038