ETO-2 associates with SCL in erythroid cells and megakaryocytes and provides repressor functions in erythropoiesis

Anna H Schuh, Alex J Tipping, Allison J Clark, Isla Hamlett, Boris Guyot, Francesco J Iborra, Patrick Rodriguez, John Strouboulis, Tariq Enver, Paresh Vyas, Catherine Porcher

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10235-50
Number of pages16
JournalMolecular and Cellular Biology
Volume25
Issue number23
DOIs
Publication statusPublished - Dec 2005

Keywords

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

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