A highly conserved intronic sequence is involved in transcriptional regulation of the alpha 1(I) collagen gene.
The first intron of the human alpha 1(I) collagen gene contains a positive, orientation-dependent cis-acting sequence located between bases +292 and +670. Transient transfection experiments indicate that this sequence is functional in both primary chicken tendon fibroblasts and in a human fibroblast-like cell line derived from SV40-transformed marrow stromal cells. DNase I footprint, methylation interference, and mobility shift analyses provide evidence for a sequence-specific binding activity and show that the region of binding corresponds to a 29-base-pair sequence that is also present in the rat alpha 1(I) collagen intron. This conserved sequence contains an AP1 consensus motif. Sequence-specific binding activity is present in nuclear extracts from HeLa and fibroblast cell lines but not in extracts from two lymphoid cell lines. Mutation of the AP1 consensus sequence indicates that this motif is required for function of the cis-acting element. These data indicate that transcriptional modulation of the alpha 1(I) collagen gene involves an interaction between an intronic AP1-containing sequence and its cognate transcription factors.
Liska
D J
DJ
Department of Biochemistry, University of Washington, Seattle 98195.
Slack
J L
JL
Bornstein
P
P
D000818:Animals; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology; D013006:Growth Hormone / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000502:physiology; D007739:L Cells; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D013006:Growth Hormone; D003094:Collagen