A Role for Dna Hypomethylation and Histone Acetylation in Maintaining Allele-specific Expression of Mouse Nkg2a in Developing and Mature Nk Cells.
From: Terry Fox Laboratory, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, Canada.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jul 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 1
- Pages: 414-21
- Medium: Print
- Language: English
- Citation (JAMA): Rogers Sally L, Rouhi Arefeh, Takei Fumio, et al. A Role for Dna Hypomethylation and Histone Acetylation in Maintaining Allele-specific Expression of Mouse Nkg2a in Developing and Mature Nk Cells.. J. Immunol. Jul 2006;177:414-21
Abstract
The repertoire of receptors that is expressed by NK cells is critical for their ability to kill virally infected or transformed cells. However, the molecular mechanisms that determine whether and when NK receptor genes are transcribed during hemopoiesis remain unclear. In this study, we show that hypomethylation of a CpG-rich region in the mouse NKG2A gene is associated with transcription of NKG2A in ex vivo NK cells and NK cell lines. This observation was extended to various developmental stages of NK cells sorted from bone marrow, in which we demonstrate that the CpGs are methylated in the NKG2A-negative stages (hemopoietic stem cells, NK progenitors, and NKG2A-negative NK cells), and hypomethylated specifically in the NKG2A-positive NK cells. Furthermore, we provide evidence that DNA methylation is important in maintaining the allele-specific expression of NKG2A. Finally, we show that acetylated histones are associated with the CpG-rich region in NKG2A positive, but not negative, cell lines, and that treatment with the histone deacetylase inhibitor trichostatin A alone is sufficient to induce NKG2A expression. Treatment with the methyltransferase inhibitor 5-azacytidine only is insufficient to induce transcription, but cotreatment with both drugs resulted in a significantly greater induction, suggesting a cooperative role for DNA methylation and histone acetylation status in regulating gene expression. These results enhance our understanding of the formation and maintenance of NK receptor repertoires in developing and mature NK cells.
Mesh Headings (Keywords): Acetylation, Alleles, Animals, Azacitidine, Base Sequence, Cell Differentiation, Cell Line, Tumor, Cells, Cultured, Chromatin, CpG Islands, Crosses, Genetic, DNA Methylation, Gene Expression Regulation, Gene Silencing, Histones, Humans, Hybrid Cells, Killer Cells, Natural, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Receptors, Immunologic, Transcription Initiation Site
Check for Full Text / PubMed Unique Identifier (PMID): 16785537
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