TY - JOUR
T1 - The minor MHC class I gene UDA of ducks is regulated by let-7 MicroRNA
AU - Chan, Wing Fuk
AU - Parks-Dely, Julie A.
AU - Magor, Brad G.
AU - Magor, Katharine E.
N1 - Funding Information:
This work was supported by Natural Sciences and Engineering Research Council of Canada Grants 2010-228035 and RGPIN 2015-05045 (to K.E.M.) and RGPIN2015-06345 (to B.G.M.).
Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/8/15
Y1 - 2016/8/15
N2 - In many nonmammalian vertebrates, the genomic organization of the MHC class I region leads to biased expression of a single classical MHC class I gene coevolving with TAP transporters, whereas class I genes are poorly expressed. This contrasts to the three codominantly expressed classical MHC class I genes in humans and mice. In a sequenced haplotype from White Pekin duck, Anas platyrhynchos, there is one predominantly expressed MHC class I, UAA, although they have five MHC class I genes in the complex, arranged TAP1-TAP2-UAA-UBA-UCA-UDA-UEA. The UAA gene, situated proximal to the TAP2 gene, is expressed at levels 10-fold greater than that of another expressed gene, UDA. Three duck MHC class I genes (UBA, UCA, and UEA) are predicted to be partially or completely inactivated by promoter defects, introduction of in-frame stop codon, or the lack of a polyadenylation signal. In this study, we confirm that UBA, UCA, and UEA are indeed inactivated through genetic defects at the promoter, whereas UAA and UDA have functionally equivalent promoters. To examine promoter accessibility, we performed bisulfite sequencing and show that none of the MHC class I promoters are inactivated by methylation. We determine that UDA is differentially regulated through its 39 untranslated region. Namely, expression of UDA is downregulated by let-7 microRNA, whereas the predominantly expressed MHC class I UAA is not. Regulation of UDA by let-7 microRNA suggests that the lower expression level is maintained for its function in immunity.
AB - In many nonmammalian vertebrates, the genomic organization of the MHC class I region leads to biased expression of a single classical MHC class I gene coevolving with TAP transporters, whereas class I genes are poorly expressed. This contrasts to the three codominantly expressed classical MHC class I genes in humans and mice. In a sequenced haplotype from White Pekin duck, Anas platyrhynchos, there is one predominantly expressed MHC class I, UAA, although they have five MHC class I genes in the complex, arranged TAP1-TAP2-UAA-UBA-UCA-UDA-UEA. The UAA gene, situated proximal to the TAP2 gene, is expressed at levels 10-fold greater than that of another expressed gene, UDA. Three duck MHC class I genes (UBA, UCA, and UEA) are predicted to be partially or completely inactivated by promoter defects, introduction of in-frame stop codon, or the lack of a polyadenylation signal. In this study, we confirm that UBA, UCA, and UEA are indeed inactivated through genetic defects at the promoter, whereas UAA and UDA have functionally equivalent promoters. To examine promoter accessibility, we performed bisulfite sequencing and show that none of the MHC class I promoters are inactivated by methylation. We determine that UDA is differentially regulated through its 39 untranslated region. Namely, expression of UDA is downregulated by let-7 microRNA, whereas the predominantly expressed MHC class I UAA is not. Regulation of UDA by let-7 microRNA suggests that the lower expression level is maintained for its function in immunity.
UR - http://www.scopus.com/inward/record.url?scp=84983761111&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1600332
DO - 10.4049/jimmunol.1600332
M3 - Article
C2 - 27430716
AN - SCOPUS:84983761111
VL - 197
SP - 1212
EP - 1220
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -