Beta-arrestin1 regulates zebrafish hematopoiesis through binding to YY1 and relieving polycomb group repression.
Beta-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.
Mesh Terms:
Animals, Arrestins, Genes, Homeobox, Hematopoiesis, Homeodomain Proteins, Repressor Proteins, Signal Transduction, YY1 Transcription Factor, Zebrafish, Zebrafish Proteins
Animals, Arrestins, Genes, Homeobox, Hematopoiesis, Homeodomain Proteins, Repressor Proteins, Signal Transduction, YY1 Transcription Factor, Zebrafish, Zebrafish Proteins
Cell
Date: Oct. 30, 2009
PubMed ID: 19879840
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