Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein.
We have previously reported that the CDX1 homeoprotein interacts with the TATA-box binding protein (TBP) on the promoter of the glucose-6-phosphatase (G6Pase) gene. We show here that CDX1 interacts with TBP via the homeodomain and that the transcriptional activity additionally requires the N-terminal domain upstream of the homeodomain. CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery. Transcription luciferase assays performed using an altered-specificity mutant of TBP provide evidence for the functionality of the interaction between CDX1 and TBP. Unlike CDX1, CDX2 does not interact with TBP nor does it transactivate the G6Pase promoter. Swapping experiments between the domains of CDX1 and CDX2 indicate that, despite opposite functional effects of the homeoproteins on the G6Pase promoter, the N-terminal domains and homeodomains of both CDX1 and CDX2 have the intrinsic ability to activate transcription and to interact with TBP. However, the carboxy domains define the specificity of CDX1 and CDX2. Thus, intra-molecular interactions control the activity and partner recruitment of CDX1 and CDX2, leading to different molecular functions.
Calon
Alexandre
A
INSERM, U682 and University Louis Pasteur, Strasbourg, France.
Gross
Isabelle
I
Davidson
Irwin
I
Kedinger
Michèle
M
Duluc
Isabelle
I
Domon-Dell
Claire
C
Freund
Jean-Noël
JN
D001665:Binding Sites; D000071616:CDX2 Transcription Factor; D002460:Cell Line; D005952:Glucose-6-Phosphatase / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D005952:Glucose-6-Phosphatase