Does Sc1-70 modulate collagen production in systemic sclerosis?
Sc1-70, an autoantigen in systemic sclerosis, may accelerate collagen gene transcription by virtue of its activity as a topoisomerase I (topo I), a DNA template-modifying enzyme. A survey of sequences corresponding to all or part of the known topo I binding sequence AGAACTTAGAGAAAATTTAAA in four fibrillar collagen genes (three of them dermal) and sixteen non-collagen genes showed a striking preponderance of the tetramer 5'-CTTA-3', comprising the core of this binding sequence, at the exon-intron junctions of the fibrillar collagen genes (59% compared with 16% in the control group). In addition, a non-random clustering of three potential topo I binding sites was seen within 350 base-pairs of 5' flanking DNA in the dermal collagen gene alpha 2(I), and a fourth site occurred in the promoter region of the alpha 1(III) gene. The findings suggest that a selective vulnerability to the action of Sc1-70/topo I is built into the structure of the dermal collagen genes.
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000032:analysis*; D001665:Binding Sites; D002356:Cartilage / Q000032:analysis; D002874:Chromosome Mapping; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D004264:DNA Topoisomerases, Type I; D005796:Genes; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000032:analysis*; D012595:Scleroderma, Systemic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000032:analysis; D014158:Transcription, Genetic
D001324:Autoantigens; D009687:Nuclear Proteins; C048100:Scl 70 antigen, human; D003094:Collagen; D004264:DNA Topoisomerases, Type I