title: DNA binding and transactivating properties of the paired and homeobox protein Pax4.
abstract: Transcription factors Pax-4 and Pax-6 are known to be key regulators of pancreatic cell differentiation and development. We report on the cloning of a mouse Pax-4 gene, which contains 10 exons, spanning a 4. 7-kbp region. The gene-targeting experiments revealed that Pax-4 and Pax-6 cannot substitute for each other in tissue with overlapping expression of both genes. We identified DNA-binding specificities of Pax-4 paired domain and paired-type homeodomain. Despite the different Pax-4 amino acid residues in positions responsible for Pax-6 paired-domain specificity, the DNA-binding specificities of Pax-4 and Pax-6 are similar. The Pax-4 homeodomain was shown to preferentially dimerize on DNA sequences consisting of an inverted TAAT motif, separated by 4-nucleotide spacing. The Pax-4 transactivation domain was localized within its C-terminal region, which transactivated GAL-based reporter 2.5-fold less than the C-terminal region of Pax-6. We believe that Pax-4 can act as a Pax-6 "repressor," due to the competition for binding sites and lower transactivation potential of Pax-4.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Anna@biomed.cas.cz
authors.forename: A
authors.initials: A
authors.lastname: Kalousová
authors.forename: V
authors.initials: V
authors.lastname: Benes
authors.forename: J
authors.initials: J
authors.lastname: Paces
authors.forename: V
authors.initials: V
authors.lastname: Paces
authors.forename: Z
authors.initials: Z
authors.lastname: Kozmik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005136:Eye Proteins; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007438:Introns; D007668:Kidney / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D008156:Luciferases