Interaction, cooperative promoter modulation, and renal colocalization of GCMa and Pitx2.
The transcription factor GCMa is a member of a new small family of transcription factors with a conserved zinc-containing DNA-binding domain. All members of this transcription factor family play crucial roles as master regulators during development. GCMa is restricted to placenta during development and to kidney and thymus at postnatal stages. It is essential for the formation of the placental labyrinth and as a consequence for survival of the embryo from mid-embryogenesis onwards. Here, we identify Pitx transcription factors as GCMa-interacting proteins. We show that Pitx proteins interact via their conserved homeodomain with the DNA-binding domain of GCMa. As a consequence, Pitx proteins and GCMa exhibit cooperative DNA binding. Furthermore, Pitx proteins influence GCMa-dependent promoter activation in a cell-specific manner. One of the three Pitx paralogues in mice, Pitx2, is the predominant Pitx member present in the placenta and colocalizes on the cellular level with GCMa in the kidney. This is the first description of a regulatory cross-talk between a transcription factor of the GCM family and a homeodomain protein.
Schubert
Steffen W
SW
Institut für Biochemie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
Kardash
Elena
E
Khan
Muhammad Amir
MA
Cheusova
Tatiana
T
Kilian
Karin
K
Wegner
Michael
M
Hashemolhosseini
Said
S
D000818:Animals; D004247:DNA / Q000378:metabolism; D000939:Epitopes; D018398:Homeodomain Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D000097577:Homeobox Protein PITX2
D004247:DNA; D000939:Epitopes; D018398:Homeodomain Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2