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Regulation of HLA class II genes expression
 Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee) ; Slavčev, Antonij (referee)
HLA class II genes are known to be highly polymorphic, even in the regulatory non-coding gene regions. Polymorphism in the promoter region potentially forms a strong basis for an uneven allele-specific expression. Even though it is known that the amount of HLA class II molecules on the cell surface has a significant role in shaping immune response, HLA class II expression polymorphism has not yet been thoroughly measured. The thesis aims to shed light into allele-specific mRNA expression and promoter DNA methylation of HLA class II genes. Two studies, each addressing different aspects of the HLA class II allele expression regulation, were conducted. Study A examines the DNA methylation of 10 DQA1 promoter and its effect on the DQA1 mRNA expression. DNA methylation in whole blood cells was determined with bisulfite sequencing and mRNA expression was measured using RT-qPCR. Even though inter-allelic differences in overall methylation were observed (the most methylated alleles were DQA1*02:01 and *04:01), the expected negative correlation between the DQA1 promoter DNA methylation density and the allele expression was not observed. We suggest that the genetic polymorphism in the region (especially region upstream of position -400, which is almost completely methylated in all alleles) may lead to different...
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