Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.
The genomic organization of a gamma-interferon-inducible gene, IP-10, reveals three introns that interrupt the transcribed sequence into four functional domains. Comparison of the intron-exon structure of this gene to the gene for an homologous chemotactic platelet protein, platelet factor 4, establishes that both genes are interrupted in precisely the same positions within homologous codons; this demonstrates that they belong to a gene family that evolved from a common ancestor. IP-10 and PF4 are two members of a newly described gene family that is likely to include the homologous chemotactic and mitogenic platelet basic proteins (connective tissue-activating protein III and beta-thromboglobulin), the transformation-related protein 9E3, and 310c, a mitogen-stimulated leukocyte protein. A DNase I-hypersensitive site has been found in responsive cells in a region upstream of the RNA initiation site. This hypersensitive site is induced by gamma interferon and thus provides a structural basis for the transcriptional activation seen for this gene by gamma interferon.
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Dewitt Wallace Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D002843:Chromatin / Q000648:ultrastructure; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000502:physiology; D017471:Receptors, Interferon; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology
D002843:Chromatin; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D007371:Interferon-gamma; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I