Cell-specific action and mutable structure of a transcription factor effector domain.
POU proteins are cell-specific transcription factors whose specificity of action has been attributed to protein-DNA and protein-protein interactions mediated by their DNA-binding (POU) domains. Here we report that transcriptional activation by SCIP, a POU protein expressed by developing Schwann cells, is dependent on an amino-terminal effector domain and that this domain mediates cell-specific transactivation in the complete absence of the POU domain. When fused to a heterologous DNA-binding domain, this SCIP domain is a potent transactivator in Schwann cells but is inactive in three heterologous cell types. The primary structure of the SCIP amino-terminal domain is novel but contains a polymorphic string of alanine residues similar to those found in several other transcription factors. Although previously hypothesized to be important for transcription factor activity, we find that the SCIP string is functionally irrelevant. We propose that homopolymers of alanine, and certain other amino acids, do not represent a motif required for transcription factor function but instead reflect regions of unstable DNA related to those associated with four recently characterized human genetic disorders.
Monuki
E S
ES
Molecular Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037.
Kuhn
R
R
Lemke
G
G
D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D017931:DNA Primers; D011994:Recombinant Proteins; D014157:Transcription Factors; D000409:Alanine