KTF-1, a transcriptional activator of Xenopus embryonic keratin expression.
Nuclear extracts from embryos of Xenopus laevis were shown to contain a protein activity, KTF-1, which binds in vitro to the promoter of the embryonic, epidermis-specific keratin gene, XK81A1. Mobility shift assays, methylation interference and footprinting analysis were used to show that the KTF-1 binding site contains an imperfect, palindromic sequence, ACCCTGAGGCT. This sequence occurs once in the XK81A1 promoter, 152-162 base pairs upstream of the transcription start site. A construct of the keratin gene in which this sequence was altered so that it no longer binds KTF-1 in vitro showed severely reduced transcription levels upon injection into Xenopus embryos, but retained epidermal specificity. Addition of KTF-1 binding sites also enhanced epidermal and non-epidermal activity of a heterologous promoter, Xenopus beta-globin, in embryos. These results suggest that KTF-1 is a general activator of embryonic keratin transcription, which acts in concert with other factors to produce high levels of epidermis-specific expression.
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
A M
AM
Snape
E A
EA
Jonas
T D
TD
Sargent
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014982:Xenopus laevis
D014157:Transcription Factors; D007633:Keratins; D004247:DNA