|ZFIN ID: ZDB-PUB-091120-6|
Beta-arrestin1 regulates zebrafish hematopoiesis through binding to YY1 and relieving polycomb group repression
Yue, R., Kang, J., Zhao, C., Hu, W., Tang, Y., Liu, X., and Pei, G.
|Source:||Cell 139(3): 535-546 (Journal)|
|Keywords:||DEVBIO, DNA, PROTEINS|
|PubMed:||19879840 Full text @ Cell|
Yue, R., Kang, J., Zhao, C., Hu, W., Tang, Y., Liu, X., and Pei, G. (2009) Beta-arrestin1 regulates zebrafish hematopoiesis through binding to YY1 and relieving polycomb group repression. Cell. 139(3):535-546.
ABSTRACTBeta-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 beta-arrestin1 as an evolutionarily conserved protein essential for zebrafish development. Zebrafish embryos depleted of beta-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 beta-arrestin1, while injection of cdx4, hoxa9a or hoxb4a mRNA rescued the hematopoietic defects. Further mechanistic studies revealed that beta-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 beta-arrestin1 during zebrafish primitive hematopoiesis, as well as an important regulator of PcG proteins and cdx4-hox pathway.