| Autor: |
Schuh, Anna H., Tipping, Alex J., Clark, Allison J., Hamlett, Isla, Guyot, Boris, Iborra, Francesco J., Rodriguez, Patrick, Strouboulis, John, Enver, Tariq, Vyas, Paresh, Porcher, Catherine |
| Předmět: |
|
| Zdroj: |
Molecular & Cellular Biology; Dec2005, Vol. 25 Issue 23, p10235-10250, 16p, 3 Diagrams, 5 Graphs |
| Abstrakt: |
Lineage specification and cellular maturation require coordinated regulation of gene expression programs. In large part, this is dependent on the activator and repressor functions of protein complexes associated with tissue-specific transcriptional regulators. In this study, we have used a proteomic approach to characterize multiprotein complexes containing the key hematopoietic regulator SCL in erythroid and megakaryocytic cell lines. One of the novel SCL-interacting proteins identified in both cell types is the transcriptional corepressor ETO-2. Interaction between endogenous proteins was confirmed in primary cells. We then showed that SCL complexes are shared but also significantly differ in the two cell types. Importantly, SCL/ETO-2 interacts with another corepressor, Gfi-1b, in red cells but not megakaryocytes. The SCL/ETO-2/Gfi-1b association is lost during erythroid differentiation of primary fetal liver cells. Genetic studies of erythroid cells show that ETO-2 exerts a repressor effect on SCL target genes. We suggest that, through its association with SCL, ETO-2 represses gene expression in the early stages of erythroid differentiation and that alleviation/modulation of the repressive state is then required for expression of genes necessary for terminal erythroid maturation to proceed. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
