The Third Human Homolog of a Murine Gene Encoding an Inhibitor of Stem Cell Proliferation Is Truncated and Linked to a CpG Island-Containing Upstream Sequence

摘要

ABSTRACTThe murine gene,MIP1α, encodes a cytokine (macrophage inflammatory protein 1α) that inhibits the proliferation of bone marrow stem cells. Two human homologs have been characterized,G0S19-1andG0S19-2. LikeMIP1α, these genes contain three exons, the first of which encodes a hydrophobic signal sequence. The existence of a third humanG0S19gene, present in one in four individuals, has been predicted from restriction enzyme analyses. This paper reports that a previously identified human genomic clone containing aG0S19sequence (G0S19-3), corresponds to the third gene. However, the firstG0S19exon is missing. The sequence differs from those ofG0S19-1andG0S19-2upstream of a point 31 nucleotides from the junction of the first intron with the second exon. This upstream sequence contains a CpG island and is named "CpG island-containing upstream sequence,"CUS. Apart from theG0S19-3-associated copy found only in individuals with the thirdG0S19gene, all individuals have one DNA species hybridizing strongly to aCUS-specific probe and at least two less strongly hybridizing species. TheCUShas potential binding sites for transcription factors AP-1, AP-2, AP-3, AP-4, and Sp1, a Donehower conserved repetitive element, and motifs characteristic of cytokine, oncogene, and retroviral promoters. Thus, theCUSmight promote the transcription of sequences with which it became associated. We suggest that theCUS-G0S19-3sequence was generated by recombination between aG0S19-2gene and a member of a novelCUS-associated gene fami