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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.

Original publication

DOI

10.1128/MCB.25.23.10235-10250.2005

Type

Journal article

Journal

Mol Cell Biol

Publication Date

12/2005

Volume

25

Pages

10235 - 10250

Keywords

Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cells, Cultured, Erythroid Cells, Erythropoiesis, Gene Expression Regulation, Megakaryocytes, Mice, Mutation, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Regulatory Sequences, Nucleic Acid, Repressor Proteins, T-Cell Acute Lymphocytic Leukemia Protein 1, Transcription Factors, Transcription, Genetic