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The highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes

TitleThe highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes
Publication TypeJournal Article
Year of Publication1999
AuthorsWheat, W, Fitzsimmons, D, Lennox, H, Krautkramer, SR, Gentile, LN, McIntosh, LP, Hagman, J
JournalMolecular and Cellular Biology
Volume19
Pagination2231-2241
Date PublishedMar
Type of ArticleArticle
ISBN Number0270-7306
KeywordsB-CELL-DEVELOPMENT, BOX, GENE, HMG DOMAIN, MURINE ETS-1, POINT MUTATION, STRUCTURAL BASIS, TRANSCRIPTION FACTORS, V-ETS, WAARDENBURG-SYNDROME
Abstract

Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a beta-hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins of the Ets proto-oncogene family to bind a composite DNA site that is essential for efficient transcription of the early-B-cell-specific mb-1 promoter. Here, evidence is provided for specific interactions between Ets-1 and the amino-terminal subdomains of Pax proteins. By tethering deletion fragments of Pax-5 to a heterologous DNA-binding domain, we show that 73 amino acids (amino acids 12 to 84) of its amino-terminal subdomain can recruit the ETS domain of Ets-1 to bind the composite site. Furthermore, an amino acid (Gln22) within the highly conserved beta-hairpin motif of Pax-5 is essential for efficient recruitment of Ets-1. The ability to recruit Ets proteins to bind DNA is a shared property of Pax proteins, as demonstrated by cooperative DNA binding of Ets-1 with sequences derived from the paired domains of Pax-2 and Pax-3. The strict conservation of sequences required for recruitment of Ets proteins suggests that Pax-Ets interactions are important for regulating transcription in diverse tissues during cellular differentiation.

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