The delta-crystallin enhancer-binding protein delta EF1 is a repressor of E2-box-mediated gene activation

R Sekido, K Murai, J Funahashi, Y Kamachi, A Fujisawa-Sehara, Y Nabeshima, H Kondoh

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Abstract

The repressor delta EF1 was discovered by its action on the DC5 fragment of the lens-specific delta 1-crystallin enhancer. C-proximal zinc fingers of delta EF1 were found responsible for binding to the DC5 fragment and had specificity to CACCT as revealed by selection of high-affinity binding sequences from a random oligonucleotide pool. CACCT is present not only in DC5 but also in the E2 box (CACCTG) elements which are the binding sites of various basic helix-loop-helix activators and also the target of an unidentified repressor, raising the possibility that delta EF1 accounts for the E2 box repressor activity. delta EF1 competed with E47 for binding to an E2 box sequence in vitro. In lymphoid cells, endogenous delta EF1 activity as a repressor was detectable, and exogenous delta EF1 repressed immunoglobulin kappa enhancer by binding to the kappa E2 site. Moreover, delta EF1 repressed MyoD-dependent activation of the muscle creatine kinase enhancer and MyoD-induced myogenesis of 10T1/2 cells. Thus, delta EF1 counteracts basic helix-loop-helix activators through binding site competition and fulfills the conditions of the E2 box repressor. In embryonic tissues, the most prominent site of delta EF1 expression is the myotome. Myotomal expression as well as the above results argues for a significant contribution of delta EF1 in regulation of embryonic myogenesis through the modulation of the actions of MyoD family proteins.

Original languageEnglish
Pages (from-to)5692-700
Number of pages9
JournalMolecular and Cellular Biology
Volume14
Issue number9
Publication statusPublished - Sep 1994

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Keywords

  • Base Sequence
  • Binding Sites
  • Consensus Sequence
  • Crystallins
  • DNA-Binding Proteins
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Genes, Immunoglobulin
  • Homeodomain Proteins
  • Immunoglobulin kappa-Chains
  • Molecular Sequence Data
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Repressor Proteins
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Zinc Fingers

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