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.
Date: 2009
Source: Cell   139(3): 535-546 (Journal)
Registered Authors:
Keywords: DEVBIO, DNA, PROTEINS
Microarrays: GEO:GSE17773
MeSH Terms:
  • Animals
  • Arrestins/metabolism*
  • Genes, Homeobox
  • Hematopoiesis*
  • Homeodomain Proteins/metabolism
  • Polycomb-Group Proteins
  • Repressor Proteins/metabolism*
  • Signal Transduction*
  • YY1 Transcription Factor/metabolism*
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 19879840 Full text @ Cell
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ABSTRACT
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.
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