Evidence for high bi-allelic expression of activating Ly49 receptors.
Stochastic expression is a hallmark of the Ly49 family that encode the main MHC class-I-recognizing receptors of mouse natural killer (NK) cells. This highly polygenic and polymorphic family includes both activating and inhibitory receptor genes and is one of genome's fastest evolving loci. The inhibitory Ly49 genes are expressed in a stochastic mono-allelic manner, possibly under the control of an upstream bi-directional early promoter and show mono-allelic DNA methylation patterns. To date, no studies have directly addressed the transcriptional regulation of the activating Ly49 receptors. Our study shows differences in DNA methylation pattern between activating and inhibitory genes in C57BL/6 and F1 hybrid mouse strains. We also show a bias towards bi-allelic expression of the activating receptors based on allele-specific single-cell RT-PCR in F1 hybrid NK cells for Ly49d and Ly49H expression in Ly49h(+/-) mice. Furthermore, we have identified a region of high sequence identity with possible transcriptional regulatory capacity for the activating Ly49 genes. Our results also point to a likely difference between NK and T-cells in their ability to transcribe the activating Ly49 genes. These studies highlight the complex regulation of this rapidly evolving gene family of central importance in mouse NK cell function.
Rouhi
Arefeh
A
The Terry Fox laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
Lai
C Benjamin
CB
Cheng
Tammy P
TP
Takei
Fumio
F
Yokoyama
Wayne M
WM
Mager
Dixie L
DL
D020121:5' Untranslated Regions; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; C527092:Klra4 protein, mouse; C527096:Klra8 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A