Twin of I-POU: a two amino acid difference in the I-POU homeodomain distinguishes an activator from an inhibitor of transcription.
I-POU, a POU domain nuclear protein that lacks two conserved basic amino acids of the POU homeodomain is coexpressed in the developing Drosophila nervous system with a second POU domain transcription factor, Cf1-a. I-POU does not bind to DNA but forms a POU domain-mediated, high affinity heterodimer with Cf1-a, inhibiting its ability to bind and activate the dopa decarboxylase gene. The I-POU/Cf1-a dimerization interface encompasses only the N-terminal basic region and helices 1 and 2 of the POU homeodomains with precise amino acid and alpha-helical requirements. twin of I-POU, an alternatively spliced transcript of the I-POU gene, encodes a protein containing the two basic amino acid residues absent in I-POU. Twin of I-POU is incapable of dimerizing with Cf1-a, but can act as a positive transcription factor on targets distinct from those regulated by Cf1-a. These findings suggest that the I-POU genomic locus simultaneously generates both a specific activator and inhibitor of gene transcription, capable of modulating two distinct regulatory programs during neural development.
Treacy
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MN
Eukaryotic Regulatory Biology Program, University of California, San Diego School of Medicine, La Jolla 92093-0648.
Neilson
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Turner
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EE
He
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Rosenfeld
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MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D005801:Genes, Homeobox / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050809:POU Domain Factors; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C066030:USP protein, Drosophila; C068431:acj6 protein, Drosophila