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Nucleic Acids Research Advance Access published online on July 15, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp592
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gene Regulation, Chromatin and Epigenetics

Evidence for high bi-allelic expression of activating Ly49 receptors

Arefeh Rouhi1, C. Benjamin Lai1,2, Tammy P. Cheng3, Fumio Takei1,4, Wayne M. Yokoyama3 and Dixie L. Mager1,2,*

1The Terry Fox laboratory, British Columbia Cancer Agency, 2Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada, 3Howard Hughes Medical Institute, Rheumatology Division, Washington University School of Medicine, St Louis, MO 63110, USA and 4Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

*To whom correspondence should be addressed. Tel: +604 675 8139; Fax: +604 877 0712; Email: dmager{at}bccrc.ca

Received April 4, 2009. Revised May 28, 2009. Accepted June 27, 2009.

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.


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