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PMID:18063754

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Citation

Sugiyama, D, Tanaka, M, Kitajima, K, Zheng, J, Yen, H, Murotani, T, Yamatodani, A and Nakano, T (2008) Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation. Blood 111:1924-32

Abstract

Friend of GATA-1 (FOG-1) is a binding partner of GATA-1, a zinc finger transcription factor with crucial roles in erythroid, megakaryocytic, and mast-cell differentiation. FOG-1 is indispensable for the function of GATA-1 during erythro/megakaryopoiesis, but FOG-1 is not expressed in mast cells. Here, we analyzed the role of FOG-1 in mast-cell differentiation using a combined experimental system with conditional gene expression and in vitro hematopoietic induction of mouse embryonic stem cells. Expression of FOG-1 during the progenitor period inhibited the differentiation of mast cells and enhanced the differentiation of neutrophils. Analysis using a mutant of PU.1, a transcription factor that positively or negatively cooperates with GATA-1, revealed that this lineage skewing was caused by disrupted binding between GATA-1 and PU.1, which is a prerequisite for mast-cell differentiation. However, FOG-1 expression in mature mast cells brought approximately a reversible loss of the mast-cell phenotype. In contrast to the lineage skewing, the loss of the mast-cell phenotype was caused by down-regulation of MITF, a basic helix-loop-helix transcription factor required for mast-cell differentiation and maturation. These results indicate that FOG-1 inhibits mast-cell differentiation in a differentiation stage-dependent manner, and its effects are produced via different molecular mechanisms.

Links

PubMed Online version:10.1182/blood-2007-08-104489

Keywords

Cell Differentiation; Colony-Forming Units Assay; DNA Primers; Embryonic Stem Cells/cytology; Embryonic Stem Cells/physiology; Flow Cytometry; GATA1 Transcription Factor/genetics; GATA1 Transcription Factor/physiology; Humans; Mast Cells/cytology; Mast Cells/physiology; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Stromal Cells/cytology; Stromal Cells/physiology; Transcription Factors/genetics; Transcription Factors/physiology

Significance

Annotations

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

MOUSE:FOG1

involved_in

GO:0032091: negative regulation of protein binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOG1

involved_in

GO:0060377: negative regulation of mast cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SPI1

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17679

F

Seeded From UniProt

complete

MOUSE:GATA1

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17433

F

Seeded From UniProt

complete

MOUSE:SPI1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17679

F

Seeded From UniProt

complete


See also

References

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