The 5′ promoter region of MHC class I chain‐related gene B

Abstract

In this study, the 5' promoter region of MHC class I chain-related gene B (MICB) was investigated in 104 healthy, unrelated Han individuals recruited from northern China, using polymerase chain reaction (PCR)-sequencing methodology. Fifteen variable sites were detected, which showed a mosaic pattern of significant global linkage disequilibrium (LD). Eleven different 5' promoter haplotypes were identified. MICB 5' promoter haplotype-9 carrying CT deletion at positions -139/-138, which is associated with decreased MICB promoter activity, was present in 26.9% of MICB alleles and was linked to MICB*002:01, MICB*008, and MICB*014 in this population. In addition, rs3828913 (position -176) and rs3828914 (position -152) were located adjacent to HSRE and GC box in MICB promoter, respectively. Sixteen extended haplotypes (EH) incorporating the MICB 5' promoter and MICB coding region were observed in this population, eight of which were in significant LD. Phylogenetic analysis of 5' promoter refined MICB sub-lineage structure indicated that MICB*005:02, the most common MICB allele, consists of five sub-lineages. Ewens-Watterson homozygosity statistics at MICB 5' promoter region were consistent with neutral expectations. Our study has shed new insight into MICB genetic variation at population level, suggesting that binding sites for transcription factors in MICB promoter could be interrupted by polymorphisms within this region, resulting in allele-specific regulation. The data will facilitate the understanding of regulation of MICB gene transcription, and will inform studies of evolution of the major histocompatibility complex (MHC) gene complex.

Further diversity of the 5′ promoter region of the MHC class I‐related chain B gene

“…. This sample was originally typed as MICB-P9, the most common promoter sequence, and typed for the coding region (exon 2-6) as MICB*008 which has been associated to MICB-P9 in other studies (Cox et al, 2014;Pan et al, 2014). The second promoter sequence named MICB-P14 was seen in CB39 sample (Indian, South-East Asian) typed previously as MICB-P9, P11 for the promoter region and MICB*002:01, 003 for MICB gene.…”

“…MICB‐P9 is shown to be the most common promoter and previous studies described it as the ancestral promoter sequence (Cox et al ., ; Pan et al ., ). The fact that we are describing three different sequences similar to MICB‐P9 indicates that MICB promoter region is very polymorphic and evolving.…”

“…The promoter regions of the MIC family were thought to be invariant for MICA promoter region and slightly polymorphic for MICB promoter (Eagle et al, 2006) until previous studies described 14 polymorphisms in MICA promoter (Cox et al, 2014;Luo et al, 2014;Laza-Briviesca et al, 2015) and 13 different sequences for MICB promoter region (Cox et al, 2014;Pan et al, 2014).…”

MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection

“…MICB genes exhibit considerable polymorphism among individuals and studies have investigated allelic association with disease (37)(38)(39). The MICB SNP rs3828913 (position -176) is located adjacent to the heat-shock response element and the GC box in the MICB promoter (40), and plays a role in transcriptional activation of the MICB gene. Previous studies reported that IFN-α stimulates MICB expression in DCs, leading to activation of NK cells, which play an important role in host antiviral activity.…”

Two novel 5′ promoter sequences of the MHC class I‐related chain A gene

“…It is known that promoters of some NKG2D ligand genes are polymorphic Pan et al, 2014), but until recently, the MICA promoter was thought to be conserved. It is now apparent that MICA promoter sequences are variable (Cox et al, 2014;Luo et al, 2014), and MICB promoters are considerably more polymorphic that previously thought (Cox et al, 2014;Pan et al, 2014), with potential functional implications due to putative differences in expression levels.…”