Transcriptional control of murine CD94 gene: differential usage of dual promoters by lymphoid cell types.
The CD94 gene product is involved in controlling NK cell activation, and is one of a family of immune receptors that is found in the NK gene complex in both humans and mice, adjacent to members of the NKG2 family. CD94 forms a heterodimeric complex with several members of the NKG2 family on the surface of NK, T, and NKT cells. These complexes recognize the nonclassical MHC class I molecules HLA-E and Qa-1(b) in humans and mice, respectively. The mechanism for cell type-specific expression of CD94 and other genes from the NK gene complex has not yet been elucidated. In the current study, we show that the murine CD94 gene has two promoters, one of which is upstream of a previously unidentified exon. We illustrate by quantitative real-time PCR that lymphoid cell types use these two promoters differentially and that the promoter usage seen in adult cells is already established during fetal development. We determined that the differential promoter usage by NK cells appears to be susceptible to perturbation, as both the murine NK cell line LNK, as well as cultured C57BL/6 NK cells showed altered promoter usage relative to fresh NK cells. Furthermore, the promoter activity observed in transfection assays did not correlate with expression of the endogenous CD94 gene, suggesting the involvement of chromatin structure/methylation in transcriptional regulation. Our detection of DNase I hypersensitive sites at the CD94 locus that are present only in a cell line expressing endogenous CD94 supports this hypothesis.
Wilhelm
Brian T
BT
Terry Fox Laboratory, British Columbia Cancer Agency, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Landry
Josette-Renée
JR
Takei
Fumio
F
Mager
Dixie L
DL
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005091:Exons / Q000276:immunology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011401:Promoter Regions, Genetic / Q000276:immunology*; D013045:Species Specificity; D014158:Transcription, Genetic / Q000276:immunology*
D015703:Antigens, CD; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D003850:Deoxyribonuclease I