title: The central domain of transcription factor FOXM1c directly interacts with itself in vivo and switches from an essential to an inhibitory domain depending on the FOXM1c binding site.
abstract: We have previously shown that FOXM1c can transactivate its target genes by two different mechanisms, depending on the FOXM1c binding site. In the present study, by introducing a small 46-aa deletion, we confirm that the central domain of FOXM1c is essential for transactivation of the minimal c-myc P1 and P2 promoters via their TATA boxes, but functions as an inhibitory domain on conventional FOXM1c binding sites. Thus, distinct FOXM1c binding sites determine opposite functions of the central domain, suggesting allosteric control of its conformation by the DNA binding site. This is strongly supported by the identification of a direct in vivo interaction of the central domain with itself in the present study. In contrast, the DNA binding domain binds neither to itself nor to any other domain of FOXM1c. Transrepression by the central domain is unlikely to be achieved by recruitment of co-repressors, but instead seems to be mediated by direct interference with the basal transcription complex. Direct binding of the central domain to itself should be involved in transrepression. Finally, FOXM1c transactivates the chicken mim-1 promoter, whose TATA box represents a conventional FOXM1c binding site, so that transactivation follows neither of the above two mechanisms, but shows intermediate behavior.
authors.affiliation: Institute of Molecular Biology, Medical School Hannover, Germany. iwiwiwi@web.de
authors.forename: Inken
authors.initials: I
authors.lastname: Wierstra
authors.forename: Jürgen
authors.initials: J
authors.lastname: Alves
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; D004247:DNA