Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15.
CD94 is a C-type lectin required for the dimerization of the CD94/NKG2 family of receptors, which are expressed on NK cells and T cell subsets. Little is known about CD94 gene expression and the elements that regulate CD94 transcription. In this study, we report that CD94 gene expression is regulated by distal and proximal promoters that transcribe unique initial exons specific to each promoter. This results in two species of transcripts; the previously described CD94 mRNA and a novel CD94C mRNA. All NK cells and CD94(+), CD8(+) alphabeta T cells transcribe CD94 mRNA. Stimulation of NK and CD8(+) alphabeta T cells with IL-2 or IL-15 induced the transcription of CD94C mRNA. The distal and proximal promoters both contain elements with IFN-gamma-activated and Ets binding sites, known as GAS/EBS. Additionally, an unknown element, termed site A, was identified in the proximal promoter. EMSA analyses showed that constitutive factors could bind to oligonucleotide probes containing each element. After treatment of primary NK cells with IL-2 or IL-15, separate inducible complexes could be detected with oligonucleotide probes containing either the proximal or distal GAS/EBS elements. These elements are highly conserved between mice and humans, which suggests that both species regulate CD94 gene expression via mechanisms that predate their evolutionary divergence.
Lieto
Louis D
LD
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Borrego
Francisco
F
You
Chi-Hyun
CH
Coligan
John E
JE
D020121:5' Untranslated Regions / Q000032:analysis; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D020218:Response Elements / Q000276:immunology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D020121:5' Untranslated Regions; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D019409:Interleukin-15; D007376:Interleukin-2; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors