Promoter sequences confirm the three different evolutionary lineages described for HLA-G

Martı́nez-Laso, Jorge; Herráiz, M.; Peñaloza, J.; Barbolla, Maria Luz; Jurado, María; Macedo, Jacqueline; Vidart, José Antonio; Cervera, Isabel

doi:10.1016/j.humimm.2012.11.016

Cited by 12 publications

(15 citation statements)

References 39 publications

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“…Data from the 1000 Genomes project, including 1092 individuals from 14 different populations, showed 32 variable sites within 1500 nucleotides upstream to the first translated ATG. Most of these variable sites have been already described in other populations or samples different from those evaluated by the 1000 Genomes consortium [6–9, 77–81]. Of those, 24 variable sites present frequencies higher than 1% and 14 present frequencies higher than 10% in the global 1000 Genomes data (all 1092 individuals).…”

Section: Hla-g Transcriptional Regulationmentioning

confidence: 84%

“…Considering that HLA-G is expressed on the surface of placenta trophoblast cells, allowing the fetus to properly develop despite the maternal immune response, some sort of functional conservation was expected. On the other hand, gene regulatory regions present several polymorphic sites close to nucleotide sequences that serve as gene regulatory elements [6–9]. Nucleotide variability in the promoter region may influence HLA-G levels by modifying binding affinity for transcription factors.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional and Posttranscriptional Regulations of theHLA-GGene

Castelli

Veiga‐Castelli

Yaghi

et al. 2014

Journal of Immunology Research

150

180

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HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.

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Section: Hla-g Transcriptional Regulationmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Transcriptional and Posttranscriptional Regulations of theHLA-GGene

Castelli

Veiga‐Castelli

Yaghi

et al. 2014

Journal of Immunology Research

150

180

View full text Add to dashboard Cite

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“…All these variants have been described in previous studies. 9,12,20 The investigation of 5′URR HLA-G sequences in 1089 individuals from 14 worldwide populations (Supplementary Figure S1) generated by the 1000 Genomes (1KG) project 32 allowed the identification of five new variants. All of these variants occurred at low frequencies in all individual populations (minor allele frequency (MAF)o 0.06).…”

Section: Resultsmentioning

confidence: 99%

“…Another sequencing survey of HLA-G 5′URR concerned a 1151-bp fragment spanning nucleotides from − 1399 to − 1049 and from − 764 to +35 in 100 individuals from Southeastern Brazil (Ribeirão Preto, State of São Paulo). 12 Other previously published data were not included in the present analysis because of (a) a lack of information on the ethnicity of sampled individuals, 69 (b) a selection bias when defining the individuals to be sequenced for the HLA-G promoter region, 18 (c) a lack of frequency data provided in the published paper 19,20 and (d) a lack of allele frequency data for SNVs with MAFo0.02. 4,28 LD, tagging and haplotype analyses Strength of LD between pairs of markers was measured as D' 70 using the Haploview software v4.2, 71 and statistical significance of LD was assessed by a Fisher's exact test of LD using the Arlequin v.3.5.1.2 software.…”

Section: Data Retrievalmentioning

confidence: 99%

“…7,8 In contrast, the HLA-G 5′URR has been poorly studied. Only a few reports have surveyed sequence variation in this gene region in healthy individuals, 4,9,12,[18][19][20][21] providing limited knowledge of the worldwide genetic diversity at this regulatory gene segment. Similarly, there have been few attempts to associate HLA-G 5′URR variations with modulation of HLA-G expression and susceptibility to diseases.…”

Section: Introductionmentioning

confidence: 99%

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Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

et al. 2014

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Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes

Arnaiz‐Villena

Suárez-Trujillo

Juárez

et al. 2022

Cell. Mol. Life Sci.

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Classical HLA (Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms have been established yet. HLA-G immune modulation gene (and also -E and -F) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained by HLA classical genes, i.e., no pathogenesis may be discovered after many years of a great amount of researchers’ effort. Thus, we believe that it is necessary to follow different research methodologies: (1) to approach this problem, based on how evolution has worked maintaining together a cluster of immune-related genes (the MHC) in a relatively short chromosome area since amniotes to human at least, i.e., immune regulatory genes (MHC-G, -E and -F), adaptive immune classical class I and II genes, non-adaptive immune genes like (C2, C4 and Bf) (2); in addition to using new in vitro models which explain pathogenetics of HLA and disease associations. In fact, this evolution may be quite reliably studied during about 40 million years by analyzing the evolution of MHC-G, -E, -F, and their receptors (KIR—killer-cell immunoglobulin-like receptor, NKG2—natural killer group 2-, or TCR-T-cell receptor—among others) in the primate evolutionary lineage, where orthology of these molecules is apparently established, although cladistic studies show that MHC-G and MHC-B genes are the ancestral class I genes, and that New World apes MHC-G is paralogous and not orthologous to all other apes and man MHC-G genes. In the present review, we outline past and possible future research topics: co-evolution of adaptive MHC classical (class I and II), non-adaptive (i.e., complement) and modulation (i.e., non-classical class I) immune genes may imply that the study of full or part of MHC haplotypes involving several loci/alleles instead of single alleles is important for uncovering HLA and disease pathogenesis. It would mainly apply to starting research on HLA-G extended haplotypes and disease association and not only using single HLA-G genetic markers.

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Promoter sequences confirm the three different evolutionary lineages described for HLA-G

Cited by 12 publications

References 39 publications

Transcriptional and Posttranscriptional Regulations of theHLA-GGene

Transcriptional and Posttranscriptional Regulations of theHLA-GGene

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes

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