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.
Eukaryotic Regulatory Biology Program, University of California, San Diego School of Medicine, La Jolla 92093-0648.
M N
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Treacy
L I
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Neilson
E E
EE
Turner
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He
M G
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Rosenfeld
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