Intragenic CpG Islands and Their Impact on Gene Regulation

Cain, James A.; Montibus, Bertille; Oakey, Rebecca J.

doi:10.3389/fcell.2022.832348

Cited by 22 publications

(12 citation statements)

References 76 publications

(90 reference statements)

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“…CGi are often localized in genes’ promoters and usually not methylated. Conversely, CGi associated with intra- or inter-genic regions can be methylated or not methylated [ 31 , 32 ]. This leads to a heterogeneous epigenetic landscape.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic analyses in forensic medicine: future and challenges

Gerra,

Dallabona,

Cecchi

2024

Int J Legal Med

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The possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be inherited or accumulated throughout a lifetime and be reversible, prompting investigation of their use across various fields. In forensic sciences, multiple applications have been proposed, such as the discrimination of monozygotic twins, identifying the source of a biological trace left at a crime scene, age prediction, determination of body fluids and tissues, human behavior association, wound healing progression, and determination of the post-mortem interval (PMI). Despite all these applications, not all the studies considered the impact of PMI and post-sampling effects on the epigenetic modifications and the tissue-specificity of the epigenetic marks.This review aims to highlight the substantial forensic significance that epigenetics could support in various forensic investigations. First, basic concepts in epigenetics, describing the main epigenetic modifications and their functions, in particular, DNA methylation, histone modifications, and non-coding RNA, with a particular focus on forensic applications, were covered. For each epigenetic marker, post-mortem stability and tissue-specificity, factors that should be carefully considered in the study of epigenetic biomarkers in the forensic context, have been discussed. The advantages and limitations of using post-mortem tissues have been also addressed, proposing directions for these innovative strategies to analyze forensic specimens.

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Section: Resultsmentioning

confidence: 99%

Epigenetic analyses in forensic medicine: future and challenges

Gerra,

Dallabona,

Cecchi

2024

Int J Legal Med

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“…Hypermethylation of gene-body CpGs can induce activation of transcription, yet the role of intragenic CpG islands is more complex and not fully understood. These regions, if hypermethylated can also inhibit gene transcription and have functions similar to promotor or enhancer regions [ 46 ]. Downstream analysis of AHRR function showed no impact on cell proliferation, rather proteomic studies revealed upregulation of proteins associated with epithelial-mesenchymal transition following AHRR KD.…”

Section: Discussionmentioning

confidence: 99%

AHRR and SFRP2 in primary versus recurrent high-grade serous ovarian carcinoma and their prognostic implication

Monjé,

Dragomir,

Sinn

et al. 2024

Br J Cancer

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Background The aim of this study was to analyse transcriptomic differences between primary and recurrent high-grade serous ovarian carcinoma (HGSOC) to identify prognostic biomarkers. Methods We analysed 19 paired primary and recurrent HGSOC samples using targeted RNA sequencing. We selected the best candidates using in silico survival and pathway analysis and validated the biomarkers using immunohistochemistry on a cohort of 44 paired samples, an additional cohort of 504 primary HGSOCs and explored their function. Results We identified 233 differential expressed genes. Twenty-three showed a significant prognostic value for PFS and OS in silico. Seven markers (AHRR, COL5A2, FABP4, HMGCS2, ITGA5, SFRP2 and WNT9B) were chosen for validation at the protein level. AHRR expression was higher in primary tumours (p < 0.0001) and correlated with better patient survival (p < 0.05). Stromal SFRP2 expression was higher in recurrent samples (p = 0.009) and protein expression in primary tumours was associated with worse patient survival (p = 0.022). In multivariate analysis, tumour AHRR and SFRP2 remained independent prognostic markers. In vitro studies supported the anti-tumorigenic role of AHRR and the oncogenic function of SFRP2. Conclusions Our results underline the relevance of AHRR and SFRP2 proteins in aryl-hydrocarbon receptor and Wnt-signalling, respectively, and might lead to establishing them as biomarkers in HGSOC.

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“…Our approach was downregulated genes with CGIs but is important to announce that DNMT3B overexpression also was related to the up-regulation of several genes. The methylation in intragenic CGIs 51 is related to cell differentiation 52 , 95 , active transcription, and enrichment of histone modifications such as H3K36me3 50 . We studied genes possibly related to the catalytic DNMT3B function, and a limitation of our study is that we can’t discriminate whether the change observed in all the deregulated genes is a catalytic or accessory function of DNMT3B 96 , we specifically tested the catalytic function in the 4 selected genes.…”

Section: Discussionmentioning

confidence: 99%

DNMT3B overexpression downregulates genes with CpG islands, common motifs, and transcription factor binding sites that interact with DNMT3B

Loaeza-Loaeza

Cerecedo-Castillo

Rodríguez-Ruiz

et al. 2022

Sci Rep

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DNA methylation is a key epigenetic modification to regulate gene expression in mammalian cells. Abnormal DNA methylation in gene promoters is common across human cancer types. DNMT3B is the main de novo methyltransferase enhanced in several primary tumors. How de novo methylation is established in genes related to cancer is poorly understood. CpG islands (CGIs), common sequences, and transcription factors (TFs) that interact with DNMT3B have been associated with abnormal de novo methylation. We initially identified cis elements associated with DNA methylation to investigate the contribution of DNMT3B overexpression to the deregulation of its possible target genes in an epithelial cell model. In a set of downregulated genes (n = 146) from HaCaT cells with DNMT3B overexpression, we found CGI, common sequences, and TFs Binding Sites that interact with DNMT3B (we called them P-down-3B). PPL1, VAV3, IRF1, and BRAF are P-down-3B genes that are downregulated and increased their methylation in DNMT3B presence. Together these findings suggest that methylated promoters aberrantly have some cis elements that could conduce de novo methylation by DNMT3B.

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Intragenic CpG Islands and Their Impact on Gene Regulation

Cited by 22 publications

References 76 publications

Epigenetic analyses in forensic medicine: future and challenges

Epigenetic analyses in forensic medicine: future and challenges

AHRR and SFRP2 in primary versus recurrent high-grade serous ovarian carcinoma and their prognostic implication

DNMT3B overexpression downregulates genes with CpG islands, common motifs, and transcription factor binding sites that interact with DNMT3B

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