1. ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis
- Author
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Catherine Porcher, Francesco J. Iborra, Alex J. Tipping, Boris Guyot, Patrick Rodriguez, Allison J. Clark, Anna Schuh, John Strouboulis, Paresh Vyas, Tariq Enver, Isla Hamlett, Cell biology, and Laviron, Nathalie
- Subjects
Cell type ,Transcription, Genetic ,Cellular differentiation ,Gene Expression ,Repressor ,Regulatory Sequences, Nucleic Acid ,Biology ,Mice ,Erythroid Cells ,Proto-Oncogene Proteins ,hemic and lymphatic diseases ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Erythropoiesis ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Molecular Biology ,Cells, Cultured ,T-Cell Acute Lymphocytic Leukemia Protein 1 ,Regulation of gene expression ,Activator (genetics) ,Nuclear Proteins ,Cell Differentiation ,Cell Biology ,Molecular biology ,Repressor Proteins ,Haematopoiesis ,Gene Expression Regulation ,Mutation ,Megakaryocytes ,Corepressor ,Protein Binding ,Transcription Factors - Abstract
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.
- Published
- 2005