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.
Yue
Rui
R
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai 200031, China.
Kang
Jiuhong
J
Zhao
Cong
C
Hu
Wenxiang
W
Tang
Yawei
Y
Liu
Xiaosong
X
Pei
Gang
G
D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D005801:Genes, Homeobox; D006410:Hematopoiesis; D018398:Homeodomain Proteins / Q000378:metabolism; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D050986:YY1 Transcription Factor / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins
D019390:Arrestins; D018398:Homeodomain Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D029961:Zebrafish Proteins; D000071557:beta-Arrestins; C499644:cdx4 protein, zebrafish