Regulation of the human SIX3 gene promoter.
A 2-kb promoter fragment of SIX3, a human transcription factor essential for vertebrate eye development, has been characterized in a gene reporter assay system. The peak of activity implies the 2-kb sequence of SIX3, whereas 5'-deletion constructs of the promoter decreases successively to 60% of the activity starting from the entire promoter. In contrast, cutting off 300 bp of the 3' promoter extinguishes its activity completely. Coexpression experiments of different other transcription factors illuminate the regulation of SIX3 during eye development: Pax6 activates the -703/-349 SIX3 promoter threefold, and PROX1 even eightfold. In contrast, Msx2 represses the entire SIX3 promoter. Furthermore, Six3 is regulated by its own negative feedback loop. In conclusion, SIX3 expression underlies a complex regulation, which is an important part to understand the network of transcription factors during eye development.
Lengler
J
J
Institute of Mammalian Genetics, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany.
Graw
J
J
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D005123:Eye / Q000254:growth & development; D005136:Eye Proteins; D005784:Gene Amplification; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D000097607:Homeobox Protein SIX3; D000098551:Prospero-Related Homeobox 1 Protein
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D000097607:Homeobox Protein SIX3; D000098551:Prospero-Related Homeobox 1 Protein; C084119:MSX2 protein; C000605730:PAX6 protein, human