Epigenetics最新文献

{"title":"Evaluating the utility of <i>ZNF331</i> promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).","authors":"Elizabeth S Nakasone, Tyler J Zemla, Ming Yu, She Yu Lin, Fang-Shu Ou, Kelly Carter, Federico Innocenti, Leonard Saltz, William M Grady, Stacey A Cohen","doi":"10.1080/15592294.2024.2349980","DOIUrl":"10.1080/15592294.2024.2349980","url":null,"abstract":"<p><p>While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of <i>ZNF331</i> promoter hypermethylation (m<i>ZNF331</i>) as a prognostic and predictive marker in colon cancer. We examined the association of m<i>ZNF331</i> with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. <i>ZNF331</i> promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of m<i>ZNF331</i> in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. m<i>ZNF331</i> was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with m<i>ZNF331</i> compared to unmethylated <i>ZNF331</i> (unm<i>ZNFF31</i>). There was no significant difference in disease-free or overall survival between patients with m<i>ZNF331</i> versus unm<i>ZNF331</i> colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by <i>ZNF331</i> methylation status. While <i>ZNF331</i> promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of m<i>ZNF331</i> as a prognostic and predictive marker.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2349980"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic editing of <i>BRCA1</i> promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells.","authors":"Wanhong He, Haijun Zhu, Sufen Zhang, Guang Shu, Han Lei, Maonan Wang, Gang Yin, Xiaohua Ni, Qihan Wu","doi":"10.1080/15592294.2024.2357518","DOIUrl":"10.1080/15592294.2024.2357518","url":null,"abstract":"<p><p>Drug resistance is the primary contributor to the high mortality rate of ovarian cancer (OC). The loss of <i>BRCA1</i>/2 function is linked to drug sensitivity in OC cells. The aim of this study is to enhance the drug sensitivity of OC cells by inducing <i>BRCA1</i> dysfunction through promoter epigenetic editing. Epigenetic regulatory regions within the <i>BRCA1</i> promoter, affecting gene expression, were initially discerned through analysis of clinical samples. Subsequently, we designed and rigorously validated epigenetic editing tools. Ultimately, we evaluated the cisplatin and olaparib sensitivity of the OC cells after editing. The <i>BRCA1</i> promoter contains two CpG-rich regions, with methylation of the region covering the transcription start site (TSS) strongly correlating with transcription and influencing OC development, prognosis, and homologous recombination (HR) defects. Targeting this region in OC cells using our designed epigenetic editing tools led to substantial and persistent DNA methylation changes, accompanied by significant reductions in H3K27ac histone modifications. This resulted in a notable suppression of <i>BRCA1</i> expression and a decrease in HR repair capacity. Consequently, edited OC cells exhibited heightened sensitivity to cisplatin and olaparib, leading to increased apoptosis rates. Epigenetic inactivation of the <i>BRCA1</i> promoter can enhance cisplatin and olaparib sensitivity of OC cells through a reduction in HR repair capacity, indicating the potential utility of epigenetic editing technology in sensitization therapy for OC.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2357518"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection.","authors":"Chunxiao Bu, Zhilong Wang, Xianping Lv, Yanteng Zhao","doi":"10.1080/15592294.2024.2374988","DOIUrl":"10.1080/15592294.2024.2374988","url":null,"abstract":"<p><p>Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2^-ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2374988"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET1 displays catalytic and non-catalytic functions in the adult mouse cortex.","authors":"Yee Hoon Foong, Blake Caldwell, Joanne L Thorvaldsen, Christopher Krapp, Clementina A Mesaros, Wanding Zhou, Rahul M Kohli, Marisa S Bartolomei","doi":"10.1080/15592294.2024.2374979","DOIUrl":"10.1080/15592294.2024.2374979","url":null,"abstract":"<p><p>TET1/2/3 dioxygenases iteratively demethylate 5-methylcytosine, beginning with the formation of 5-hydroxymethylcytosine (5hmC). The post-mitotic brain maintains higher levels of 5hmC than most peripheral tissues, and TET1 ablation studies have underscored the critical role of TET1 in brain physiology. However, deletion of <i>Tet1</i> precludes the disentangling of the catalytic and non-catalytic functions of TET1. Here, we dissect these functions of TET1 by comparing adult cortex of <i>Tet1</i> wildtype (<i>Tet1</i> WT), a novel <i>Tet1</i> catalytically dead mutant (<i>Tet1</i> HxD), and <i>Tet1</i> knockout (<i>Tet1</i> KO) mice. Using DNA methylation array, we uncover that <i>Tet1</i> HxD and KO mutations perturb the methylation status of distinct subsets of CpG sites. Gene ontology (GO) analysis on specific differential 5hmC regions indicates that TET1's catalytic activity is linked to neuronal-specific functions. RNA-Seq further shows that <i>Tet1</i> mutations predominantly impact the genes that are associated with alternative splicing. Lastly, we performed High-performance Liquid Chromatography Mass-Spectrometry lipidomics on WT and mutant cortices and uncover accumulation of lysophospholipids lysophosphatidylethanolamine and lysophosphatidylcholine in <i>Tet1</i> HxD cortex. In summary, we show that <i>Tet1</i> HxD does not completely phenocopy <i>Tet1</i> KO, providing evidence that TET1 modulates distinct cortical functions through its catalytic and non-catalytic roles.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2374979"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA.","authors":"Thu N A Doan, James M Cowley, Aaron L Phillips, Jessica F Briffa, Shalem Y Leemaqz, Rachel A Burton, Tania Romano, Mary E Wlodek, Tina Bianco-Miotto","doi":"10.1080/15592294.2023.2294516","DOIUrl":"10.1080/15592294.2023.2294516","url":null,"abstract":"<p><p>Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase <i>Dnmt3a</i> and the imprinted genes <i>Cdkn1c</i> (Cyclin-dependent kinase inhibitor 1C) and <i>Kcnq1</i> (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA <i>Kcnq1ot1</i> (<i>Kcnq1</i> opposite strand/antisense transcript 1). <i>Kcnq1ot1</i> expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between <i>Kcnq1ot1</i> and <i>Kcnq1</i> in the E20 growth restricted group (Spearman's <i>ρ =</i> 0.014). No correlation was observed between <i>Kcnq1ot1</i> and <i>Cdkn1c</i> expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2294516"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide meta-analysis of prenatal vitamin D insufficiency and cord blood DNA methylation.","authors":"Elizabeth W Diemer, Johanna Tuhkanen, Sara Sammallahti, Kati Heinonen, Alexander Neumann, Sonia L Robinson, Matthew Suderman, Jianping Jin, Christian M Page, Ruby Fore, Sheryl L Rifas-Shiman, Emily Oken, Patrice Perron, Luigi Bouchard, Marie France Hivert, Katri Räikköne, Jari Lahti, Edwina H Yeung, Weihua Guan, Sunni L Mumford, Maria C Magnus, Siri Håberg, Wenche Nystad, Christine L Parr, Stephanie J London, Janine F Felix, Henning Tiemeier","doi":"10.1080/15592294.2024.2413815","DOIUrl":"10.1080/15592294.2024.2413815","url":null,"abstract":"<p><p>Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring's health in later life. We aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was conditionally associated with DNA methylation in the offspring cord blood. Maternal vitamin D insufficiency (plasma 25-hydroxy vitamin D <math><mo>≤</mo></math> 75 nmol/L) during pregnancy and offspring cord blood DNA methylation, assessed using Illumina Infinium 450k or Illumina EPIC Beadchip, was collected for 3738 mother-child pairs in 7 cohorts as part of the Pregnancy and Childhood Epigenetics (PACE) consortium. Associations between maternal vitamin D and offspring DNA methylation, adjusted for fetal sex, maternal smoking, maternal age, maternal pre-pregnancy or early pregnancy BMI, maternal education, gestational age at measurement of 25(OH)D, parity, and cell type composition, were estimated using robust linear regression in each cohort, and a fixed-effects meta-analysis was conducted. The prevalence of vitamin D insufficiency ranged from 44.3% to 78.5% across cohorts. Across 364,678 CpG sites, none were associated with maternal vitamin D insufficiency at an epigenome-wide significant level after correcting for multiple testing using Bonferroni correction or a less conservative Benjamini-Hochberg False Discovery Rate approach (FDR, <i>p</i> > 0.05). In this epigenome-wide association study, we did not find convincing evidence of a conditional association of vitamin D insufficiency with offspring DNA methylation at any measured CpG site.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2413815"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis.","authors":"Kaimin Guo, Yin Cao, Zhiyi Zhao, Jiantao Zhao, Lingyun Liu, Hongliang Wang","doi":"10.1080/15592294.2024.2381849","DOIUrl":"10.1080/15592294.2024.2381849","url":null,"abstract":"<p><p>Gametogenetin binding protein 2 (GGNBP2) was indispensable in normal spermatids for transformation into mature spermatozoa in mice, and when Gametogenetin binding protein 2 is bound to BRCC36 and RAD51, the complex participates in repairing DNA double-strand breaks (DSB) during the meiotic progression of spermatocytes. Ggnbp2 knockout resulted in the up-regulation of H2A_K119ubi and down-regulation of H2B_K120ubi in GC-2 cells (mouse spermatogonia-derived cell line) and postnatal day 18 testis lysate. Our results also demonstrated that Gametogenetin binding protein 2 inducedASXL1 to activate the deubiquitinating enzyme BAP1 in deubiquitinating H2A, while Gametogenetin binding protein 2 knockout disrupted the interaction between ASXL1 and BAP1, resulting in BAP1 localization change. Furthermore, the Gametogenetin binding protein 2 deletion reduced H2B ubiquitination by affecting E2 enzymes and E3 ligase binding. Gametogenetin binding protein 2 regulated H2A and H2B ubiquitination levels and controlled H3_K27 and H3_K79 methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3_K27trimethylation (H3_K27me3) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3_K79me2), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2381849"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic confounds of transgenerational epigenetic inheritance in mice.","authors":"Daniel M Sapozhnikov, Moshe Szyf","doi":"10.1080/15592294.2024.2318519","DOIUrl":"10.1080/15592294.2024.2318519","url":null,"abstract":"<p><p>Transgenerational epigenetic inheritance in mammals remains a controversial phenomenon. A recent study by Takahashi et al. provides evidence for this mode of inheritance in mice by using a CRISPR/Cas9-based epigenetic editing technique to modify DNA methylation levels at specific promoters and then demonstrating the inheritance of the gain in methylation in offspring. In this technical commentary, we argue that the method used in the original study inherently amplifies the likelihood of genetic changes that thereafter lead to the heritability of epigenetic changes. We provide evidence that genetic changes from multiple sources do indeed occur in these experiments and explore several avenues by which these changes could be causal to the apparent inheritance of epigenetic changes. We conclude a genetic basis of inheritance cannot be ruled out and thus transgenerational epigenetic inheritance has not been adequately established by the original study.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2318519"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-carbon metabolism nutrients impact the interplay between DNA methylation and gene expression in liver, enhancing protein synthesis in Atlantic salmon.","authors":"Takaya Saito, Marit Espe, Vibeke Vikeså, Christoph Bock, Tårn H Thomsen, Anne-Catrin Adam, Jorge M O Fernandes, Kaja H Skjaerven","doi":"10.1080/15592294.2024.2318517","DOIUrl":"10.1080/15592294.2024.2318517","url":null,"abstract":"<p><p>Supplementation of one-carbon (1C) metabolism micronutrients, which include B-vitamins and methionine, is essential for the healthy growth and development of Atlantic salmon (<i>Salmo salar</i>). However, the recent shift towards non-fish meal diets in salmon aquaculture has led to the need for reassessments of recommended micronutrient levels. Despite the importance of 1C metabolism in growth performance and various cellular regulations, the molecular mechanisms affected by these dietary alterations are less understood. To investigate the molecular effect of 1C nutrients, we analysed gene expression and DNA methylation using two types of omics data: RNA sequencing (RNA-seq) and reduced-representation bisulphite sequencing (RRBS). We collected liver samples at the end of a feeding trial that lasted 220 days through the smoltification stage, where fish were fed three different levels of four key 1C nutrients: methionine, vitamin B6, B9, and B12. Our results indicate that the dosage of 1C nutrients significantly impacts genetic and epigenetic regulations in the liver of Atlantic salmon, particularly in biological pathways related to protein synthesis. The interplay between DNA methylation and gene expression in these pathways may play an important role in the mechanisms underlying growth performance affected by 1C metabolism.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2318517"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta.","authors":"Michael Mortillo, Elizabeth G Kennedy, Karen M Hermetz, Amber A Burt, Carmen J Marsit","doi":"10.1080/15592294.2024.2326869","DOIUrl":"10.1080/15592294.2024.2326869","url":null,"abstract":"<p><p>5-hydroxymethylcystosine (5hmC), is an intermediate product in the DNA demethylation pathway, but may act as a functional epigenetic modification. We have conducted the largest study of site-specific 5hmC in placenta to date using parallel bisulphite and oxidative bisulphite modification with array-based assessment. Incorporating parallel RNA-sequencing data allowed us to assess associations between 5hmC and gene expression, using expression quantitative trait hydroxymethylation (eQTHM) analysis. We identified ~ 47,000 loci with consistently elevated (systematic) 5hmC proportions. Systematic 5hmC was significantly depleted (<i>p</i> < 0.0001) at CpG islands (CGI), and enriched (<i>p</i> < 0.0001) in 'open sea' regions (CpG >4 kb from CGI). 5hmC was most and least abundant at CpGs in enhancers and active transcription start sites (TSS), respectively (<i>p</i> < 0.05). We identified 499 significant (empirical-p <0.05) eQTHMs within 1 MB of the assayed gene. At most (75.4%) eQTHMs, the proportion of 5hmC was positively correlated with transcript abundance. eQTHMs were significantly enriched among enhancer CpGs and depleted among CpGs in active TSS (<i>p</i> < 0.05 for both). Finally, we identified 107 differentially hydroxymethylated regions (DHMRs, <i>p</i> < 0.05) across 100 genes. Our study provides insight into placental distribution of 5hmC, and sheds light on the functional capacity of this epigenetic modification in placenta.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2326869"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}