PMID:1409581

Citation	Hagman, J and Grosschedl, R (1992) An inhibitory carboxyl-terminal domain in Ets-1 and Ets-2 mediates differential binding of ETS family factors to promoter sequences of the mb-1 gene. Proc. Natl. Acad. Sci. U.S.A. 89:8889-93
Abstract	The mb-1 gene is expressed only during the early stages of B-lymphocyte differentiation. Here we show that the mb-1 proximal promoter region contains a functionally important binding site for members of the ETS family of DNA-binding proteins. We found that both the E26 virus-encoded v-ets and the myeloid/B-cell-specific factor PU.1 bind efficiently to this site in vitro. By contrast, Ets-1, the lymphocyte-specific cellular homologue of v-ets, and the related, more ubiquitously expressed Ets-2 protein interacted weakly with this binding site. DNA binding by both Ets-1 and Ets-2, however, could be increased 20- to 50-fold by deleting as few as 16 carboxyl-terminal amino acids. The inhibitory carboxyl-terminal amino acid sequence is highly conserved between Ets-1 and Ets-2 but is not present in either v-ets or PU.1. Replacement of the carboxyl-terminal amino acids of v-ets with those of Ets-1 decreased DNA binding by v-ets drastically. Cotranslation of Ets-1 transcripts encoding proteins of different lengths suggested that Ets-1 binds DNA as a monomer. Therefore, the carboxyl-terminal inhibitory domain appears to interfere directly with DNA binding and not with homodimerization. Finally, the functional relevance of ETS factor binding to the mb-1 promoter site was evidenced by the stimulation of transcription through this site by a v-myb-v-ets fusion protein. Together, these data suggest that one or more ETS family factors are involved in the regulation of mb-1 gene expression.
Links	PubMed PMC50029
Keywords	Amino Acid Sequence; Animals; B-Lymphocytes/cytology; B-Lymphocytes/physiology; Base Sequence; Binding Sites; Cell Differentiation/genetics; Chloramphenicol O-Acetyltransferase/genetics; Chloramphenicol O-Acetyltransferase/isolation & purification; Chloramphenicol O-Acetyltransferase/metabolism; DNA-Binding Proteins/metabolism; Gene Expression; Molecular Sequence Data; Multigene Family; Mutagenesis, Site-Directed; Oligodeoxyribonucleotides; Oncogenes; Promoter Regions, Genetic; Protein Biosynthesis; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Protein c-ets-2; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/isolation & purification; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-ets; Proto-Oncogenes; Recombinant Fusion Proteins/isolation & purification; Recombinant Fusion Proteins/metabolism; Repressor Proteins; Restriction Mapping; Retroviridae Proteins, Oncogenic/genetics; Retroviridae Proteins, Oncogenic/isolation & purification; Retroviridae Proteins, Oncogenic/metabolism; Trans-Activators; Transcription Factors; Transcription, Genetic
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