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Co‐operative DNA binding by GAGA transcription factor requires the conserved BTB/POZ domain and reorganizes promoter topology
Author(s) -
Katsani Katerina R.,
Hajibagheri M. A. Nasser,
Verrijzer C. Peter
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.3.698
Subject(s) - biology , transcription factor , promoter , transcription (linguistics) , dna binding domain , dna , dna binding protein , genetics , dna binding site , microbiology and biotechnology , topology (electrical circuits) , gene , gene expression , combinatorics , linguistics , mathematics , philosophy
The POZ domain is a conserved protein–protein interaction motif present in a variety of transcription factors involved in development, chromatin remodelling and human cancers. Here, we study the role of the POZ domain of the GAGA transcription factor in promoter recognition. Natural target promoters for GAGA typically contain multiple GAGA‐binding elements. Our results show that the POZ domain mediates strong co‐operative binding to multiple sites but inhibits binding to single sites. Protein cross‐linking and gel filtration chromatography experiments established that the POZ domain is required for GAGA oligomerization into higher order complexes. Thus, GAGA oligomerization increases binding specificity by selecting only promoters with multiple sites. Electron microscopy revealed that GAGA binds to multiple sites as a large oligomer and induces bending of the promoter DNA. Our results indicate a novel mode of DNA binding by GAGA, in which a large GAGA complex binds multiple GAGA elements that are spread out over a region of a few hundred base pairs. We suggest a model in which the promoter DNA is wrapped around a GAGA multimer in a conformation that may exclude normal nucleosome formation.