| First Author | Freson K | Year | 2003 |
| Journal | Hum Genet | Volume | 112 |
| Issue | 1 | Pages | 42-9 |
| PubMed ID | 12483298 | Mgi Jnum | J:82043 |
| Mgi Id | MGI:2450775 | Doi | 10.1007/s00439-002-0832-1 |
| Citation | Freson K, et al. (2003) Molecular cloning and characterization of the GATA1 cofactor human FOG1 and assessment of its binding to GATA1 proteins carrying D218 substitutions. Hum Genet 112(1):42-9 |
| abstractText | Erythroid and megakaryocytic lineage differentiation and maturation are regulated via cooperation between transcription factor GATA1 and its essential cofactor friend-of-GATA1 (FOG1). The interaction between these two murine proteins is well studied in vitro and depends on the binding of Fog1 to the N-terminal zinc finger (N-finger) of Gata1. We identified the human FOG1 gene on chromosome 16q24 and found expression mainly in hematopoietic cells and also in several other tissues. Sequencing of FOG1 cDNA revealed a 1006 amino-acid protein that contained nine zinc fingers, highly homologous to murine Fog1 fingers. The amino acid sequence and the GATA1-binding capacity of the human and murine finger 5 are however different. Ex vivo binding studies demonstrated that FOG1 interacts with both GATA1 and GATA2. We and others have described patients with mutations in the GATA1 N-finger (V205 M, D218G, D218Y, or G208S), who suffer from macrothrombocytopenia and erythrocyte abnormalities. We now show ex vivo that the interaction between GATA1 and FOG1 is indeed disturbed in platelets and erythrocytes of those patients carrying D218 GATA1 mutations. The identification of the human FOG1 gene will enable the genetic screening of patients with non X-linked thrombocytopenia and dyserythropoiesis. |
