DNA methylation at enhancer regions Novel avenues for epigenetic biomarker development

Helgason, Cheryl D.

doi:10.2741/4399

Cited by 19 publications

(12 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Methylation of gene enhancers is also involved in cell type-specific gene activation or repression by controlling transcription factor binding sites [16]. Individual gene enhancers and their epigenetic regulation in diseases are, however, still poorly understood, but experimental evidence points to a substantial role of DNA methylation [17].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

et al. 2019

View full text Add to dashboard Cite

Background Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 ( TREX2 ) locus in laryngeal ( n = 256) and colorectal cancer cases ( n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts ( p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 ( p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients ( p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies. Electronic supplementary material The online version of this article (10.1186/s13148-019-0666-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Additionally, hypomethylation and hypermethylation can regulate target gene expression by activating or silencing enhancers, respectively (Clermont et al, 2016;Ehrlich, 2019). These processes are dysregulated in many human cancers, leading to cellular de-differentiation and malignant transformation (Taberlay et al, 2014;Clermont et al, 2016). Along with 5mC, 5-hydroxymethylcytosine (5hmC) has been recently recognized as a stable modification that has multiple roles from cell pluripotency to carcinogenesis rather than merely intermedium of DNA demethylation (Putiri et al, 2014;Moen et al, 2015;López et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine

Zhou

Bissessur

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer. There are increasing evidence indicating that 5hmC in cell-free DNA play an active role during carcinogenesis. However, it remains unclear whether 5hmC could surpass classical markers in cancer detection, treatment, and prognosis. Here, we systematically reviewed the recent advances in the clinic and basic research of DNA 5-hydroxymethylation in cancer, especially in cell-free DNA. We further discuss the mechanisms underlying aberrant 5hmC patterns and carcinogenesis. Synergistically, 5-hydroxymethylation may act as a promising biomarker, unleashing great potential in early cancer detection, prognosis, and therapeutic strategies in precision oncology.

show abstract

“…CpG islands are genomic regions highly enriched in CpG sequences, and often associated with promoter regions of a gene [10]. CpG methylation located in promoters [11, 12], first exons [13], gene bodies [14–16], or enhancer elements [17] of the genome can influence the transcriptional activity of neighbouring genes, though the mechanisms by which methylation affects transcription in other genomic regions is still largely unknown. Additionally, epigenetic patterns can be transmitted to the next generation through the germline or the developing embryonic environment [18], but to what degree nutrients in the parental diet influence gene regulation in the next generation is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Profiling DNA methylation patterns of zebrafish liver associated with parental high dietary arachidonic acid

et al. 2019

View full text Add to dashboard Cite

Diet has been shown to influence epigenetic key players, such as DNA methylation, which can regulate the gene expression potential in both parents and offspring. Diets enriched in omega-6 and deficient in omega-3 PUFAs (low dietary omega-3/omega-6 PUFA ratio), have been associated with the promotion of pathogenesis of diseases in humans and other mammals. In this study, we investigated the impact of increased dietary intake of arachidonic acid (ARA), a physiologically important omega-6 PUFA, on 2 generations of zebrafish. Parental fish were fed either a low or a high ARA diet, while the progeny of both groups were fed the low ARA diet. We screened for DNA methylation on single base-pair resolution using reduced representation bisulfite sequencing (RRBS). The DNA methylation profiling revealed significant differences between the dietary groups in both parents and offspring. The majority of differentially methylated loci associated with high dietary ARA were found in introns and intergenic regions for both generations. Common loci between the identified differentially methylated loci in F 0 and F 1 livers were reported. We described overlapping gene annotations of identified methylation changes with differential expression, but based on a small number of overlaps. The present study describes the diet-associated methylation profiles across genomic regions, and it demonstrates that parental high dietary ARA modulates DNA methylation patterns in zebrafish liver.

show abstract

DNA methylation at enhancer regions Novel avenues for epigenetic biomarker development

Cited by 19 publications

References 118 publications

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine

Profiling DNA methylation patterns of zebrafish liver associated with parental high dietary arachidonic acid

Contact Info

Product

Resources

About