Epigenome Association Study for DNA Methylation Biomarkers in Buccal and Monocyte Cells for Female Rheumatoid Arthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE186179 | GEO | 2021/12/15
REPOSITORIES: GEO
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Project description:The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure. Sperm were collected to examine differential DNA methylation regions (DMR) between the exposed and control populations. A statistically significant signature of DMRs was identified in the chemotherapy exposed male sperm. The DMRs, termed epimutations, were found in CpG desert regions of primarily 1 kilobase size. Gene associations and correlations to genetic mutations (copy number variation) were also investigated. Observations indicate adolescent chemotherapy exposure can promote epigenetic alterations that persist in later life. The germline (i.e. sperm) epimutations identified suggest chemotherapy has the potential to promote epigenetic inheritance to the next generation.
2016-10-01 | GSE85790 | GEO
Project description:While tobacco smoke exposure strongly influences DNA methylation and is causative in numerous human diseases, the underlying mechanistic links are obscure. Here we investigated genome-wide smoking-associated differentially methylated regions (SM-DMRs) using CD14 monocytes of smokers (n=47) and nonsmokers (n=46) from two independently recruited populations, the Multi-Ethnic Study of Atherosclerosis (MESA) and Clinical Research Unit (CRU) at NIEHS. We found that SM-DMRs preferentially occur at genomic regions with the characteristics of putative enhancer, open chromatin, and the enrichment of TF binding indicated by ENCODE/Roadmap Epigenome/BLUEPRINT datasets. Most of our selected candidate SM-DMRs identified in the two populations were also observed in other hematopoietic cell types (CD15 granulocytes, CD19 B cells, CD4 T cells, CD8 T cells, CD56 NK cells) and were successfully validated using a second method in an independently recruited group of subjects. Aryl-Hydrocarbon Receptor Repressor (AHRR) SM-DMR, located at an intragenic enhancer, was the most significantly affected DMR and we have previously reported that a methylation level of a CpG in this gene was associated with subclinical atherosclerosis. The AHRR DMR was also detected in saliva DNA and these results were highly correlated with effects in monocytes (r2 = 0.90), suggesting that saliva may provide a potential alternative, noninvasive source for biomarkers that use DNA. Mechanistically, our results suggested that AHRR SM-DMR upregulated AHRR mRNA through activating AHRR enhancer in monocytes of smokers but not in granulocytes, indicated by increased noncoding RNA. Taken together, our study suggests that cell type-specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease.
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Project description:Utilizing reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, we have analyzed ~0.1% of CpG dinucleotides present in the human genome for imprinted differentially methylated regions (DMRs) using the Illumina Infinium HumanMethylation27 BeadChip microarray. This approach identified 15 imprinted DMRs associated with previously characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, we discovered two novel DMRs: a maternally methylated region overlapping the FAM50B promoter CpG island, which results in paternal expression of this retrotransposon, and a paternally methylated region located between maternally expressed ZNF597 and NAT15 genes. We analyzed reciprocal genome-wide uniparental disomy samples (one maternal UPD and three paternal UPD samples) and six different normal somatic tissues derived from the three germinal layers (lymphocytes, buccal cells, placenta, brain, muscle, and fat) .
2011-05-26 | E-GEOD-28525 | biostudies-arrayexpress
Project description:Plastic derived compounds are one of the most frequent daily world-wide exposures. Previously a mixture of plastic derived toxicants involving bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP) at lower dose exposures of a gestating female rat were found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation) and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations show disease specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease specific DMR associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.
2021-03-16 | GSE163412 | GEO
Project description:Although hydrogen sulfide is toxic to most organisms, a fish, Poecilia mexicana, has adapted to survive in environments with high levels of hydrogen sulfide. The epigenetic changes in response to this environmental stress were examined by assessing DNA methylation alterations in the nucleated red blood cells (RBC) in the fish. In addition to collecting wild males and females from sulfidic and non-sulfidic environments, wild males and females in these environments were collected and moved to a non-sulfidic environment in the laboratory and propagated for two generations in a non-sulfidic environment. We compared epimutations between sexes and field and laboratory populations. The F0 generation sulfidic wild fish were compared to the non-sulfidic wild fish and found to have significant differential DNA methylation regions (DMRs) in the RBC DNA. The F2 generation laboratory fish were also compared between the sulfidic and non-sulfidic populations, and a significant number of DMRs were also identified. The DMRs have stable generational inheritance in the absence of the sulfidic environment. The DMRs in the F0 generation wild fish had an over 80% overlap with the F2 generation laboratory non-sulfidic environment propagated fish. This is one of the first examples of epigenetic generational stability after the removal of an environmental stressor. The DMR associated genes were found to be relevant to sulfur toxicity and metabolism processes.
2020-12-09 | GSE157730 | GEO
Project description:Normal and two transformed buccal keratinocyte lines were cultured under a standardized condition to explore mechanisms of carcinogenesis and tumor marker expression at transcript and protein level. An approach combining three bioinformatic programs allowed coupling of abundant proteins and large-scale transcript data to low-abundance transcriptional regulators. The analysis identified previously proposed, and suggested novel, protein biomarkers, Gene Ontology categories and molecular networks including functionally impaired key regulator genes for buccal/oral carcinoma. Experiment Overall Design: Analysis of differential expression in two transformed buccal keratinocyte lines (SVpgC2a and SqCC/Y1) relative to normal buccal keratinocytes. Both normal and transformed cells were cultured under a standardized serum-free condition. Experiment Overall Design: Two replicates for all cell types were included.
2008-06-15 | E-GEOD-7862 | biostudies-arrayexpress
Project description:Normal and two transformed buccal keratinocyte lines were cultured under a standardized condition to explore mechanisms of carcinogenesis and tumor marker expression at transcript and protein level. An approach combining three bioinformatic programs allowed coupling of abundant proteins and large-scale transcript data to low-abundance transcriptional regulators. The analysis identified previously proposed, and suggested novel, protein biomarkers, Gene Ontology categories and molecular networks including functionally impaired key regulator genes for buccal/oral carcinoma. Keywords: Cell type comparison
2007-08-21 | GSE7862 | GEO
Project description:This study examined the potential transgenerational actions of the herbicide atrazine. The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease, increased frequency of tumor development in males and females (predominately mammary tumors), early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations and a lean phenotype in males and females involving a reduced adipocyte size, decreased body mass index (BMI) and reduced adiposity. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified. A comparison of control versus atrazine lineage sperm identified 519 DMRs (p<10-6) for the F1 generation, 431 DMR (p<10-5) for the F2 generation, and 958 DMR (p<10-9) for the transgenerational F3 generation sperm.
2017-08-08 | GSE98683 | GEO
Project description:A tissue like buccal mucosa (from cheek swabs) would be an ideal sample material for rapid, easy collection for testing of biomarkers as an alternative to blood. A limited number of studies, primarily in the smoker/oral cancer literature, address this tissue's efficacy for quantitative PCR or microarray gene expression analysis. In this study both qPCR and microarray analyses were used to evaluate gene expression in buccal cells. An initial study comparing blood and buccal cells from the same individuals looked at relative amounts of four genes. The RNA isolated from buccal cells was degraded but was of sufficient quality to be used with RT-qPCR to detect expression of specific genes. Second, buccal cell RNA was used for microarray-based differential gene expression studies by comparing gene expression between smokers and nonsmokers. The isolation and amplification protocol allowed use of 150-fold less buccal cell RNA than had been reported previously with human microarrays. We report here the finding of a small number of significant gene expression differences between smokers and nonsmokers, using buccal cells as target material. Additionally, Gene Set Enrichment Analysis confirmed that these genes were changing expression in the same pattern as seen in an earlier buccal cell study performed by another group. Our results suggest that in spite of a high degree of RNA degradation, buccal cells from cheek mucosa could be used to detect differential gene expression between smokers and nonsmokers. However the RNA degradation, increase in sample variability and microarray failure rate show that buccal samples should be used with caution as source material in expression studies.
2010-03-01 | GSE16149 | GEO