| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
CD94/NKG2A is an inhibitory receptor expressed by most human NK cells and a subset of T cells that recognizes HLA-E on potential target cells. To study the transcriptional regulation of the human NKG2A gene, we cloned a 3.9-kb genomic fragment that contains a 1.65-kb region upstream of the exon 1, as well as exon 1 (untranslated), intron 1 and exon 2. Using deletion mutants, we identified a region immediately upstream from the most upstream transcriptional initiation site that led to increased transcriptional activity from a luciferase reporter construct in YT-Indy (NKG2A positive) cells relative to Jurkat and K562 (both NKG2A negative) cells. We also localized a DNase I hypersensitivity site to this region. Within this 80-bp segment, we identified two GATA binding sites. Mutation of GATA binding site II (–2302 bp) but not GATA binding site I (–2332 bp) led to decreased transcriptional activity. Pull-down assays revealed that GATA-3 could bind oligonucleotide probes containing the wild type but not a mutated GATA site II. Using chromatin immunoprecipitation assays, we showed that GATA-3 specifically binds to the NKG2A promoter in situ in NKL and primary NK cells, but not in Jurkat T cells. Moreover, coexpression of human GATA-3 with an NKG2A promoter construct in K562 cells led to enhanced promoter activity, and transfection of NKL cells with small interfering RNA specific for GATA-3 reduced NKG2A cell surface expression. Taken together, our data indicate that GATA-3 is an important transcription factor for regulating NKG2A gene expression.
This article has been cited by other articles:
|
|
 |
|
  A. Saez-Borderias, N. Romo, G. Magri, M. Guma, A. Angulo, and M. Lopez-Botet IL-12-Dependent Inducible Expression of the CD94/NKG2A Inhibitory Receptor Regulates CD94/NKG2C+ NK Cell Function J. Immunol., January 15, 2009; 182(2): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Marusina, S. J. Burgess, I. Pathmanathan, F. Borrego, and J. E. Coligan Regulation of Human DAP10 Gene Expression in NK and T Cells by Ap-1 Transcription Factors J. Immunol., January 1, 2008; 180(1): 409 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cooley, F. Xiao, M. Pitt, M. Gleason, V. McCullar, T. L. Bergemann, K. L. McQueen, L. A. Guethlein, P. Parham, and J. S. Miller A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature Blood, July 15, 2007; 110(2): 578 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Welner, R. Pelayo, K. P. Garrett, X. Chen, S. S. Perry, X.-H. Sun, B. L. Kee, and P. W. Kincade Interferon-producing killer dendritic cells (IKDCs) arise via a unique differentiation pathway from primitive c-kitHiCD62L+ lymphoid progenitors Blood, June 1, 2007; 109(11): 4825 - 4931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Rogers, A. Rouhi, F. Takei, and D. L. Mager A Role for DNA Hypomethylation and Histone Acetylation in Maintaining Allele-Specific Expression of Mouse NKG2A in Developing and Mature NK Cells J. Immunol., July 1, 2006; 177(1): 414 - 421. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
