Segments of the POU domain influence one another's DNA-binding specificity

Aurora, R., Herr, W. (February 1992) Segments of the POU domain influence one another's DNA-binding specificity. Mol Cell Biol, 12 (2). pp. 455-67. ISSN 0270-7306 (Print)0270-7306 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1732727
DOI: 10.1128/MCB.12.2.455

Abstract

The ubiquitously expressed mammalian POU-domain protein Oct-1 specifically recognizes two classes of cis-acting regulatory elements that bear little sequence similarity, the octamer motif ATGCAAAT and the TAATGARAT motif. The related pituitary-specific POU protein Pit-1 also recognizes these two motifs but, unlike Oct-1, binds preferentially to the TAATGARAT motif. Yet in our assay, Pit-1 still binds octamer elements better than does the octamer motif-binding protein Oct-3. The POU domain is responsible for recognizing these diverse regulatory sequences through multiple DNA contacts that include the two POU subdomains, the POU-specific region, and the POU homeodomain. The DNA-binding properties of 10 chimeric POU domains, in which different POU-domain segments are derived from either Oct-1 or Pit-1, reveal a high degree of structural plasticity; these hybrid proteins all bind DNA well and frequently bind particular sites better than does either of the parental POU domains. In these chimeric POU domains, the POU-specific A and B boxes and the hypervariable POU linker can influence DNA-binding specificity. The surprising result is that the influence a particular segment has on DNA-binding specificity can be greatly affected by the origin of other segments of the POU domain and the sequence of the binding site. Thus, the broad but selective DNA-binding specificity of Oct-1 is conferred both by multiple DNA contacts and by dynamic interactions within the DNA-bound POU domain.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Base Sequence Binding Sites DNA/*metabolism DNA-Binding Proteins/chemistry/genetics/*metabolism Electrophoresis Escherichia coli/genetics/metabolism Gene Expression Host Cell Factor C1 Macromolecular Substances Molecular Sequence Data Octamer Transcription Factor-1 Octamer Transcription Factor-3 Plasmids/genetics Recombinant Fusion Proteins/chemistry/genetics/metabolism *Regulatory Sequences, Nucleic Acid Transcription Factor Pit-1 Transcription Factors/chemistry/genetics/*metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DNA binding protein
CSHL Authors:
Communities: CSHL labs > Herr lab
Depositing User: Matt Covey
Date: February 1992
Date Deposited: 29 Sep 2015 16:18
Last Modified: 29 Sep 2015 16:18
PMCID: PMC364190
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31821

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