Evidence for epigenetic maintenance of Ly49a monoallelic gene expression.
Although structurally unrelated, the human killer cell Ig-like (KIR) genes and the rodent lectin-like Ly49 genes serve similar functional roles in NK cells. Moreover, both gene families display variegated, monoallelic expression patterns established at the transcriptional level. DNA methylation has been shown to play an important role in maintenance of expression patterns of KIR genes, which have CpG island promoters. The potential role of DNA methylation in expression of Ly49 genes, which have CpG-poor promoters, is unknown. In this study, we show that hypomethylation of the region encompassing the Pro-2 promoter of Ly49a and Ly49c in primary C57BL/6 NK cells correlates with expression of the gene. Using C57BL/6 x BALB/c F1 hybrid mice, we demonstrate that the expressed allele of Ly49a is hypomethylated while the nonexpressed allele is heavily methylated, indicating a role for epigenetics in maintaining monoallelic Ly49 gene expression. Furthermore, the Ly49a Pro-2 region is heavily methylated in fetal NK cells but variably methylated in nonlymphoid tissues. Finally, in apparent contrast to the KIR genes, we show that DNA methylation and the histone acetylation state of the Pro-2 region are strictly linked with Ly49a expression status.
Rouhi
Arefeh
A
The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Gagnier
Liane
L
Takei
Fumio
F
Mager
Dixie L
DL
D000107:Acetylation; D000483:Alleles; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006657:Histones / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011401:Promoter Regions, Genetic / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D006657:Histones; C527088:Klra1 protein, mouse; C527091:Klra3 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like