Abstract
The LIM-only protein Lmo2, activated by chromosomal translocations in T-cell leukaemias, is normally expressed in haematopoiesis. It interacts with TAL1 and GATA-1 proteins, but the function of the interaction is unexplained. We now show that in erythroid cells Lmo2 forms a novel DNA-binding complex, with GATA-1, TAL1 and E2A, and the recently identified LIM-binding protein Ldb1/NLI. This oligomeric complex binds to a unique, bipartite DNA motif comprising an E-box, CAGGTG, followed approximately 9 bp downstream by a GATA site. In vivo assembly of the DNA-binding complex requires interaction of all five proteins and establishes a transcriptional transactivating complex. These data demonstrate one function for the LIM-binding protein Ldb1 and establish a function for the LIM-only protein Lmo2 as an obligatory component of an oligomeric, DNA-binding complex which may play a role in haematopoiesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Binding Sites
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COS Cells
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Consensus Sequence
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DNA-Binding Proteins / metabolism*
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Erythroid-Specific DNA-Binding Factors
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Genes, Reporter
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Hematopoiesis / genetics*
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LIM Domain Proteins
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Metalloproteins / metabolism
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Models, Genetic
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Nuclear Proteins / metabolism
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Protein Binding
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Proto-Oncogene Proteins*
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Regulatory Sequences, Nucleic Acid
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T-Cell Acute Lymphocytic Leukemia Protein 1
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / metabolism*
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Transcription, Genetic*
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Transcriptional Activation*
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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LDB1 protein, human
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LIM Domain Proteins
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Lmo2 protein, mouse
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Metalloproteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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T-Cell Acute Lymphocytic Leukemia Protein 1
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TCF Transcription Factors
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TCF7L1 protein, human
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Tal1 protein, mouse
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors