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PMID: 16287841 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 25 ·No. 23 ·2005-12-00 ·Pages 10235-50

Schuh AH, Tipping AJ, Clark AJ, Hamlett I, Guyot B, Iborra FJ, Rodriguez P, Strouboulis J, Enver T, Vyas P, Porcher C

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.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors/genetics,metabolism Cell Differentiation Cells, Cultured Erythroid Cells/cytology,metabolism Erythropoiesis Gene Expression Regulation Megakaryocytes/metabolism Mice Mutation/genetics Nuclear Proteins/genetics,metabolism Protein Binding Proto-Oncogene Proteins/genetics,metabolism Regulatory Sequences, Nucleic Acid Repressor Proteins/genetics,metabolism T-Cell Acute Lymphocytic Leukemia Protein 1 Transcription Factors/genetics,metabolism Transcription, Genetic/genetics
Chemicals
Basic Helix-Loop-Helix Transcription Factors Cbfa2t3 protein, mouse Gfi1b protein, mouse Nuclear Proteins Proto-Oncogene Proteins Repressor Proteins T-Cell Acute Lymphocytic Leukemia Protein 1 Tal1 protein, mouse Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Schuh Anna H
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Tipping Alex J
Clark Allison J
Hamlett Isla
Guyot Boris
Iborra Francesco J
Rodriguez Patrick
Strouboulis John
Enver Tariq
Vyas Paresh
Porcher Catherine
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.23.10235-10250.2005
Published
2005-12-00
Pages
10235-50
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1291220
Subset
IM
Grants
Medical Research Council · MC_U137973816 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.25.23.10235-10250.2005 PMC Full Text View journal details
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