Coordinate expression of the human pregnancy-specific glycoprotein gene family during induced and replicative senescence

Endoh, Morio; Kobayashi, Yusuke; Yamakami, Yoshimi; Yonekura, Ryuzo; Fujii, Michihiko; Ayusawa, Dai

doi:10.1007/s10522-008-9173-3

Cited by 11 publications

(10 citation statements)

References 40 publications

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“…The pregnancy-specific glycoprotein (PSG) gene cluster on 19q13.2 provides an especially striking example. PSG genes are abundantly expressed in the placenta during pregnancy and are vital for safeguarding the developing fetus from infectious agents in the maternal bloodstream [55, 56]. Across the 11 tandemly duplicated genes in this family, there are 24 higher-order parallelisms, including three 4-dimensional parallelisms and one parallelism involving five SNPs (Additional file 8: Figure S2).…”

Section: Resultsmentioning

confidence: 99%

Interlocus gene conversion explains at least 2.7 % of single nucleotide variants in human segmental duplications

Dumont

2015

BMC Genomics

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BackgroundInterlocus gene conversion (IGC) is a recombination-based mechanism that results in the unidirectional transfer of short stretches of sequence between paralogous loci. Although IGC is a well-established mechanism of human disease, the extent to which this mutagenic process has shaped overall patterns of segregating variation in multi-copy regions of the human genome remains unknown. One expected manifestation of IGC in population genomic data is the presence of one-to-one paralogous SNPs that segregate identical alleles.ResultsHere, I use SNP genotype calls from the low-coverage phase 3 release of the 1000 Genomes Project to identify 15,790 parallel, shared SNPs in duplicated regions of the human genome. My approach for identifying these sites accounts for the potential redundancy of short read mapping in multi-copy genomic regions, thereby effectively eliminating false positive SNP calls arising from paralogous sequence variation. I demonstrate that independent mutation events to identical nucleotides at paralogous sites are not a significant source of shared polymorphisms in the human genome, consistent with the interpretation that these sites are the outcome of historical IGC events. These putative signals of IGC are enriched in genomic contexts previously associated with non-allelic homologous recombination, including clear signals in gene families that form tandem intra-chromosomal clusters.ConclusionsTaken together, my analyses implicate IGC, not point mutation, as the mechanism generating at least 2.7 % of single nucleotide variants in duplicated regions of the human genome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1681-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Interlocus gene conversion explains at least 2.7 % of single nucleotide variants in human segmental duplications

Dumont

2015

BMC Genomics

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“…One possibility is that as epithelial cells lose their differentiated state, or are overgrown by metaplastic non-expressing cells, PSG expression becomes incidentally lost apart from in residual cells that retain some features of normal epithelial cells. Alternatively, there is evidence that senescing cells express PSGs, 30 and we speculate that there may be de novo expression of PSGs in senescing tumor cells. Loss of PSG expression in tumors may not support the use of PSGs as tumor biomarkers detectable in blood because expression in normal GI tract tissues might mask expression arising from tumors.…”

Section: Discussionmentioning

confidence: 85%

Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies

Houston

Williams

Roviš

et al. 2016

mAbs

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(2016) Pregnancyspecific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies, mAbs, 8:3, 491-500, DOI: 10.1080DOI: 10. /19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 ABSTRACTPregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members related to the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family and are encoded by 10 genes in the human. They are secreted at high levels by placental syncytiotrophoblast into maternal blood during pregnancy, and are implicated in immunoregulation, thromboregulation, and angiogenesis. To determine whether PSGs are expressed in tumors, we characterized 16 novel monoclonal antibodies to human PSG1 and used 2 that do not cross-react with CEACAMs to study PSG expression in tumors and in the gastrointestinal (GI) tract using tissue arrays and immunohistochemistry. Staining was frequently observed in primary squamous cell carcinomas and colonic adenocarcinomas and was correlated with the degree of tumor differentiation, being largely absent from metastatic samples. Staining was also observed in normal oesophageal and colonic epithelium. PSG expression in the human and mouse GI tract was confirmed using quantitative RT-PCR. However, mRNA expression was several orders of magnitude lower in the GI tract compared to placenta. Our results identify a non-placental site of PSG expression in the gut and associated tumors, with implications for determining whether PSGs have a role in tumor progression, and utility as tumor biomarkers.

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“…Among tissues, placenta had the highest SSM-based pairs of genes, including PSG1/PSG6, PSG1/PSG11, PSG1/PSG8, PSG1/PSG9 and PSG8/PSG9 pairs, which showed highly significant cp -values (< 8.10 -5 ). It is of interest to note that the common regulation between members of PSG family genes has been suggested to be related to chromatin structure [35], suggesting that epigenetic markers might be also detected by the SSM approach. Taken together, our data show that genes associated with the same biological process or expressed in the same tissue share more SSMs than random genes, thereby serving as a useful and novel marker for common regulatory mechanisms.…”

Section: Resultsmentioning

confidence: 99%

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

et al. 2011

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BackgroundRegulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods.ResultsHere, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values.ConclusionsUsing unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.

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Coordinate expression of the human pregnancy-specific glycoprotein gene family during induced and replicative senescence

Cited by 11 publications

References 40 publications

Interlocus gene conversion explains at least 2.7 % of single nucleotide variants in human segmental duplications

Interlocus gene conversion explains at least 2.7 % of single nucleotide variants in human segmental duplications

Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

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