The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells

Verloes, A.; Spits, Claudia; Vercammen, M.; Geens, Mieke; LeMaoult, Joël; Sermon, Karen; Coucke, Wim; Velde, H. Van de

doi:10.1016/j.scr.2017.01.005

Cited by 26 publications

(35 citation statements)

References 59 publications

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“…Following a similar pathway shown in HLA‐A, reduced methylation within the promoter region is the prime switch for HLA‐G expression in human embryonic stem cells (with further post‐transcriptional modification affected by microRNA binding). Methylation of the HLA‐G promoter will permit permanent silencing in other cells where its expression does not normally occur (Verloes et al, ).…”

Section: Factors Affecting Surface Expressionmentioning

confidence: 99%

“…Similarly, a 14‐bp indel in the 3′UTR of the nonclassical class I HLA‐G gene has been shown to affect stability of the HLA‐G mRNA, with the insertion resulting in a lower amount of mRNA. HLA‐G possesses variations in the 3′UTR which affects the binding site for miR‐148 and additionally miR‐152 (Carosella et al, ; Verloes et al, ).…”

Section: Factors Affecting Surface Expressionmentioning

confidence: 99%

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Factors affecting HLA expression: A review

Carey

Poulton

Poles

2019

Int J Immunogenetics

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The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)‐specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross‐match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA‐specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA‐C, HLA‐DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA‐directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA‐specific antibody, would lead to a more informed algorithm to assess transplant risk.

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Section: Factors Affecting Surface Expressionmentioning

confidence: 99%

Section: Factors Affecting Surface Expressionmentioning

confidence: 99%

Factors affecting HLA expression: A review

Carey

Poulton

Poles

2019

Int J Immunogenetics

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“…The GO enrichment analysis for the DMRs indicated that the genes were mainly enriched in the GO terms, including HES4, PRKCZ,SKI,PRDM16,ALPL,RUNX3,TAL1,TTLL7,BARHL2,OLFM3,NFYC,TBX15,LMX1A,TNFRSF4,AJAP1,SYTL1,OPRD1,PTPRU,PRRX1,ELF3,PROX1, HLA-G, and HLA-E (Table 4). Among these, we screened HLA-G (P=1.86E-30), HLA-E (P=9.42E-11), and PRDM16 (P=1.86E-30), which are closely related to embryonic development, as candidate genes of RM (Gelmini et al 2016;Horn et al 2011;Verloes et al 2017).…”

Section: Go Enrichment Analysis and Go-tree Of The Dmrsmentioning

confidence: 99%

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

2020

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Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RMrelated biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM-receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

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“…In addition to epigenetic factors, HLA-G expression is controlled by one or more inherited alleles and genetic variations in noncoding regions of the gene [93][94]. Therefore, the expression level of HLA-G after infections appears to be determined, at least in part, by the host's genetic background.…”

Section: Hla-g: Regulation Of Gene Expressionmentioning

confidence: 99%

“…In addition to factors involved at the transcriptional level, HLA-G expression is also controlled at post-transcriptional levels [102]. Although some microRNAs bind to nonpolymorphic sequences, polymorphisms in the HLA-G 3' untranslated region (3'UTR) may affect mRNA stability by changing the affinity of this region for the corresponding micoRNAs (94,102). Moreover, HLA-G expression is also affected by the level of related microRNAs.…”

Section: Hla-g: Regulation Of Gene Expressionmentioning

confidence: 99%

HLA-G: Facts and Fictions

Shahraki

Alavianmehr

Farjadian

2018

Asian Pac J Cancer Biol

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Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.

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The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells

Cited by 26 publications

References 59 publications

Factors affecting HLA expression: A review

Factors affecting HLA expression: A review

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

HLA-G: Facts and Fictions

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