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...

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Bibliographic Details
Published in:Nucleic acids research 2009-09, Vol.37 (16), p.5331-5342
Main Authors: Rouhi, Arefeh, Lai, C. Benjamin, Cheng, Tammy P., Takei, Fumio, Yokoyama, Wayne M., Mager, Dixie L.
Format: Article
Language:English
Subjects:
5' Untranslated Regions
Alleles
Animals
Base Sequence
DNA Methylation
Gene Regulation, Chromatin and Epigenetics
Mice
Mice, Inbred C57BL
Molecular Sequence Data
NK Cell Lectin-Like Receptor Subfamily A - genetics
NK Cell Lectin-Like Receptor Subfamily A - metabolism
Sequence Homology, Nucleic Acid
T-Lymphocytes - immunology
Transcription, Genetic
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkp592