PUBLICATION

Beta-arrestin1 regulates zebrafish hematopoiesis through binding to YY1 and relieving polycomb group repression

Authors
Yue, R., Kang, J., Zhao, C., Hu, W., Tang, Y., Liu, X., and Pei, G.
ID
ZDB-PUB-091120-6
Date
2009
Source
Cell   139(3): 535-546 (Journal)
Registered Authors
Keywords
DEVBIO, DNA, PROTEINS
Datasets
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
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping