Organization of the murine and human interleukin-7 receptor genes: two mRNAs generated by differential splicing and presence of a type I-interferon-inducible promoter.
To better understand the regulation of interleukin-7 receptor (IL-7R) expression, we have pursued a detailed analysis of the structure of the murine and human IL-7R genes. The genes consist of eight exons, the sizes of which are conserved in mouse and human cells, spread out over 24 kbp (murine) and 19 kbp (human). A differential splicing event results in an mRNA encoding a secreted form of the human IL-7R gene. Primer extension and S1 nuclease analysis show a single transcriptional start site for the murine IL-7R gene. The 5'-flanking region of the murine IL-7R gene contains TATA- and CAAT-like sequences. The promoter region also contains a functional interferon regulatory element, to which the interferon-induced nuclear factors IRF-1 and IRF-2 are capable of binding and which is able to confer interferon-inducible expression on a heterologous gene. There are also potential binding sites for the transcription factors AP-1 and AP-2 as well as multiple glucocorticoid response elements. A fusion gene containing 2.5 kb of murine IL-7R 5' regulatory sequence linked to the bacterial chloramphenicol acetyltransferase gene directed expression of chloramphenicol acetyltransferase activity in murine pre-B-cell line 70Z/3 but not in the mouse fibroblast cell line NIH 3T3. Comparison of the murine and human IL-7R exon/intron boundaries with those of other hematopoietin receptor superfamily members whose exon/intron boundaries are also known reveals a conserved evolutionary structure.
Pleiman
C M
CM
Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101.
Gimpel
S D
SD
Park
L S
LS
Harada
H
H
Taniguchi
T
T
Ziegler
S F
SF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D003001:Cloning, Molecular; D005091:Exons; D005260:Female; D015698:Genomic Library; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology*; D015851:Interleukin-7 / Q000378:metabolism; D008099:Liver / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010920:Placenta / Q000276:immunology; D010957:Plasmids; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D020395:Receptors, Interleukin-7; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D014158:Transcription, Genetic
D007370:Interferon Type I; D015851:Interleukin-7; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7