Chan Wing Fuk, Parks-Dely Julie A, Magor Brad G, Magor Katharine E
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and.
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and
J Immunol. 2016 Aug 15;197(4):1212-20. doi: 10.4049/jimmunol.1600332. Epub 2016 Jul 18.
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 3' 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.
在许多非哺乳类脊椎动物中，MHC I类区域的基因组组织导致与TAP转运蛋白共同进化的单个经典MHC I类基因出现偏向性表达，而其他I类基因表达水平很低。这与人类和小鼠中三个共显性表达的经典MHC I类基因形成对比。在来自北京鸭（Anas platyrhynchos）的一个测序单倍型中，尽管该复合体中有五个MHC I类基因，排列顺序为TAP1 - TAP2 - UAA - UBA - UCA - UDA - UEA，但有一个主要表达的MHC I类基因UAA。位于TAP2基因近端的UAA基因，其表达水平比另一个表达基因UDA高10倍。预测三个鸭MHC I类基因（UBA、UCA和UEA）因启动子缺陷、框内终止密码子的引入或缺乏多聚腺苷酸化信号而部分或完全失活。在本研究中，我们证实UBA、UCA和UEA确实因启动子的遗传缺陷而失活，而UAA和UDA具有功能等效的启动子。为了检测启动子的可及性，我们进行了亚硫酸氢盐测序，结果表明没有一个MHC I类启动子因甲基化而失活。我们确定UDA通过其3'非翻译区受到差异调节。具体来说，UDA的表达受到let - 7微小RNA的下调，而主要表达的MHC I类基因UAA则不受影响。let - 7微小RNA对UDA的调节表明其较低的表达水平是为了维持其免疫功能。
