PMID:10700180

Citation	Nichols, KE, Crispino, JD, Poncz, M, White, JG, Orkin, SH, Maris, JM and Weiss, MJ (2000) Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat. Genet. 24:266-70
Abstract	Haematopoietic development is regulated by nuclear protein complexes that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis in embryonic stem cells and mice has revealed roles for the X-linked gene Gata1 in erythrocyte and megakaryocyte differentiation. GATA-1 is the founding member of a family of DNA-binding proteins that recognize the motif WGATAR through a conserved multifunctional domain consisting of two C4-type zinc fingers. Here we describe a family with X-linked dyserythropoietic anaemia and thrombocytopenia due to a substitution of methionine for valine at amino acid 205 of GATA-1. This highly conserved valine is necessary for interaction of the amino-terminal zinc finger of GATA-1 with its essential cofactor, FOG-1 (for friend of GATA-1; refs 9-12). We show that the V205M mutation abrogates the interaction between Gata-1 and Fog-1, inhibiting the ability of Gata-1 to rescue erythroid differentiation in an erythroid cell line deficient for Gata-1 (G1E). Our findings underscore the importance of FOG-1:Gata-1 associations in both megakaryocyte and erythroid development, and suggest that other X-linked anaemias or thrombocytopenias may be caused by defects in GATA1.
Links	PubMed Online version:10.1038/73480
Keywords	Adult; Amino Acid Sequence; Amino Acid Substitution; Anemia, Dyserythropoietic, Congenital/genetics; Child; Consensus Sequence; Cryptorchidism/genetics; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Erythroid-Specific DNA-Binding Factors; Female; GATA1 Transcription Factor; Hematopoiesis/genetics; Humans; Infant, Newborn; Male; Models, Molecular; Molecular Sequence Data; Pedigree; Point Mutation; Protein Structure, Tertiary; Recombinant Fusion Proteins/genetics; Thrombocytopenia/congenital; Thrombocytopenia/genetics; Transcription Factors/chemistry; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology; X Chromosome/genetics; Zinc Fingers/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:GATA1	involved_in	GO:0030220: platelet formation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:GATA1	involved_in	GO:0030219: megakaryocyte differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:GATA1	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:GATA1	involved_in	GO:0008584: male gonad development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:GATA1	enables	GO:0000976: transcription regulatory region sequence-specific DNA binding	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:GATA1	involved_in	GO:0048821: erythrocyte development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:GATA1	involved_in	GO:0030218: erythrocyte differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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