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PMID:19879840

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Citation

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 139:535-46

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.

Links

PubMed Online version:10.1016/j.cell.2009.08.038

Keywords

Animals; Arrestins/metabolism; Genes, Homeobox; Hematopoiesis; Homeodomain Proteins/metabolism; Repressor Proteins/metabolism; Signal Transduction; YY1 Transcription Factor/metabolism; Zebrafish/genetics; Zebrafish/growth & development; Zebrafish/metabolism; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:C3PTE8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-030131-1117,ZFIN:ZDB-GENE-060824-1

F

Seeded From UniProt

complete

DANRE:C3PTE8

involved_in

GO:0035162: embryonic hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100311-1

P

Seeded From UniProt

complete

DANRE:C3PTE8

involved_in

GO:0048368: lateral mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100311-1

P

Seeded From UniProt

complete

HUMAN:TYY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49407

F

Seeded From UniProt

complete

HUMAN:ARRB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P25490

F

Seeded From UniProt

complete

HUMAN:ARRB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P53779

F

Seeded From UniProt

complete

HUMAN:ARRB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q00987

F

Seeded From UniProt

complete

HUMAN:MK10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49407

F

Seeded From UniProt

complete

HUMAN:MDM2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49407

F

Seeded From UniProt

complete

DANRE:Q5XJ55

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-030131-1117,ZFIN:ZDB-GENE-060824-1

F

Seeded From UniProt

complete

DANRE:Q5XJ55

involved_in

GO:0035162: embryonic hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100311-1

P

Seeded From UniProt

complete

DANRE:Q5XJ55

involved_in

GO:0048368: lateral mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100311-1

P

Seeded From UniProt

complete

DANRE:Q7T1S3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-030131-1117,ZFIN:ZDB-GENE-060824-1

F

Seeded From UniProt

complete

DANRE:T1NXD7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-030131-1117,ZFIN:ZDB-GENE-060824-1

F

Seeded From UniProt

complete


See also

References

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