EpigeneticsPub Date : 2024-12-01Epub Date: 2024-05-13DOI: 10.1080/15592294.2024.2346694
Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig
{"title":"Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress.","authors":"Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig","doi":"10.1080/15592294.2024.2346694","DOIUrl":"10.1080/15592294.2024.2346694","url":null,"abstract":"<p><p>The transgenerational effects of exposing male mice to chronic social instability (CSI) stress are associated with decreased sperm levels of multiple members of the miR-34/449 family that persist after their mating through preimplantation embryo (PIE) development. Here we demonstrate the importance of these miRNA changes by showing that restoring miR-34c levels in PIEs derived from CSI stressed males prevents elevated anxiety and defective sociability normally found specifically in their adult female offspring. It also restores, at least partially, levels of sperm miR-34/449 normally reduced in their male offspring who transmit these sex-specific traits to their offspring. Strikingly, these experiments also revealed that inducing miR-34c levels in PIEs enhances the expression of its own gene and that of miR-449 in these cells. The same induction of embryo miR-34/449 gene expression likely occurs after sperm-derived miR-34c is introduced into oocytes upon fertilization. Thus, suppression of this miRNA amplification system when sperm miR-34c levels are reduced in CSI stressed mice can explain how a comparable fold-suppression of miR-34/449 levels can be found in PIEs derived from them, despite sperm containing ~50-fold lower levels of these miRNAs than those already present in PIEs. We previously found that men exposed to early life trauma also display reduced sperm levels of miR-34/449. And here we show that miR-34c can also increase the expression of its own gene, and that of miR-449 in human embryonic stem cells, suggesting that human PIEs derived from men with low sperm miR-34/449 levels may also contain this potentially harmful defect.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2346694"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916317","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":"MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of <i>Grin2a</i> in the mouse prefrontal cortex.","authors":"Liting Xue, Jialu Zhao, Xu Liu, Tian Zhao, Ying Zhang, Haihong Ye","doi":"10.1080/15592294.2024.2417158","DOIUrl":"10.1080/15592294.2024.2417158","url":null,"abstract":"<p><p>Acute exposure to MK-801, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induces schizophrenia-like behavioural changes in juvenile male mice. However, the effects of acute MK-801 exposure on brain gene expression at the translation level remain unclear. Here, we conducted ribosome profiling analysis on the prefrontal cortex (PFC) of acute MK-801-exposed juvenile male mice. We found 357 differentially translated genes, with the <i>N</i><sup>4</sup>-acetylcytidine (ac<sup>4</sup>C) consensus motif enriched in the transcripts with increased translation efficiency. Acetylated RNA immunoprecipitation sequencing revealed 148 differentially acetylated peaks, of which 121 were hyperacetylated, and 27 were hypoacetylated. Genes harbouring these peaks were enriched in pathways related to axon guidance, Hedgehog signalling pathway, neuron differentiation, and memory. <i>Grin2a</i> encodes an NMDA receptor subunit NMDAR2A, and its human orthologue is a strong susceptibility gene for schizophrenia. <i>Grin2a</i> mRNA was hyperacetylated and exhibited significantly increased translation efficiency. NMDAR2A protein level was increased in MK-801-exposed PFC. Pretreatment of Remodelin, an inhibitor of <i>N</i>-acetyltransferase 10, returned the NMDAR2A protein levels to normal and partially reversed schizophrenia-like behaviours of MK-801-exposed mice, shedding light on the possible role of mRNA acetylation in the aetiology of schizophrenia.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2417158"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497364","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-12-03DOI: 10.1080/15592294.2024.2437272
Yu Liang, Yongbo Wang, Jia Tan, Jingxuan Shu, Ya Xu, Mingyuan Wang, Shengjun Yang, Linna Ma
{"title":"Homocysteine affects macrophage polarization by altering m6A methylation of scavenger receptors CD209 and CD163L1.","authors":"Yu Liang, Yongbo Wang, Jia Tan, Jingxuan Shu, Ya Xu, Mingyuan Wang, Shengjun Yang, Linna Ma","doi":"10.1080/15592294.2024.2437272","DOIUrl":"10.1080/15592294.2024.2437272","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory disease characterized by fatty plaque deposits on artery walls. Elevated plasma homocysteine (Hcy) levels are an independent risk factor for atherosclerosis. Research on the mechanism by which Hcy promotes atherosclerosis has gradually turned to epigenetic inheritance, but the correlation between Hcy and m6A (N6-methyladenosine) modification has not been reported. In this study, MeRIP-seq was performed on macrophages and Hcy-treated macrophages. GO and KEGG analyses were used to perform functional analysis of differentially methylated genes. qRT-PCR and western blot were taken to determine the expression of CD209, CD163L1, proinflammatory, and anti-inflammatory factors. Flow cytometry was used to detect the proportion of M2 macrophages. The results showed that after Hcy treatment, the overall m6A methylation of macrophages was down-regulated, and 856 differential methylation peaks were annotated to 781 genes. These included CD209 and CD163L1, whose m6A methylation was inhibited after treatment with Hcy. In addition, mRNA and protein expressions of CD209 and CD163L1 were also inhibited after Hcy treatment. Overexpression of CD209 or CD163L1 prevents the Hcy-induced decrease in the proportion of M2 macrophages. This article identified changes in the modification level of m6A in macrophages by Hcy and revealed the possible mechanism by which Hcy induces macrophage polarization.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2437272"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767390","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-06-20DOI: 10.1080/15592294.2024.2368995
Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima
{"title":"Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers.","authors":"Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima","doi":"10.1080/15592294.2024.2368995","DOIUrl":"10.1080/15592294.2024.2368995","url":null,"abstract":"<p><p>Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2368995"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426551","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-02-18DOI: 10.1080/15592294.2024.2309824
Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow
{"title":"Association of changes in expression of <i>HDAC</i> and <i>SIRT</i> genes after drug treatment with cancer cell line sensitivity to kinase inhibitors.","authors":"Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow","doi":"10.1080/15592294.2024.2309824","DOIUrl":"10.1080/15592294.2024.2309824","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of <i>HDAC</i> and <i>SIRT</i> genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple <i>HDAC</i> and <i>SIRT</i> genes. <i>HDAC5</i> was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of <i>HDAC5, HDAC1</i>, and several <i>SIRT</i> genes. We confirmed changes in <i>HDAC</i> and <i>SIRT</i> expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of <i>HDAC</i> and <i>SIRT</i> genes may influence chemosensitivity and may need to be considered during chemotherapy.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2309824"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899587","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":"Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.","authors":"Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang","doi":"10.1080/15592294.2023.2299044","DOIUrl":"10.1080/15592294.2023.2299044","url":null,"abstract":"<p><p>Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2299044"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058237","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-11-13DOI: 10.1080/15592294.2024.2426952
Bambarendage P U Perera, Kai Wang, Dongyue Wang, Kathleen Chen, Alisa Dewald, Swati Sriram, Jaclyn M Goodrich, Laurie K Svoboda, Maureen A Sartor, Dana C Dolinoy
{"title":"Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure.","authors":"Bambarendage P U Perera, Kai Wang, Dongyue Wang, Kathleen Chen, Alisa Dewald, Swati Sriram, Jaclyn M Goodrich, Laurie K Svoboda, Maureen A Sartor, Dana C Dolinoy","doi":"10.1080/15592294.2024.2426952","DOIUrl":"10.1080/15592294.2024.2426952","url":null,"abstract":"<p><p>Lead (Pb) is a neurotoxicant with early life exposure linked to long-term health effects. Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWIL proteins to induce DNA methylation. It remains unknown whether Pb exposure influences piRNA expression. This study evaluated how perinatal Pb exposure (32 ppm in drinking water) impacts piRNA expression in adult mice and assessed piRNA dysregulation as a potential mechanism for Pb-induced toxicity. Pb exposure effects on piRNA expression and associated gene repression in the germline (testis/ovary) and soma (liver and brain) were evaluated. Small RNA sequencing was used to determine differentially expressed piRNAs, RT-qPCR to examine piRNA target expression, and whole genome bisulfite sequencing to evaluate target DNA methylation status. Three piRNAs (mmpiR-1500602, mmpiR-0201406, and mmpiR-0200026) were significant after multiple testing correction (all downregulated in the male Pb-exposed brain in comparison to control; FDR < 0.05). Within piOxiDB, TAO Kinase 3 was identified as a downstream mRNA target for one of the three Pb-sensitive piRNA. The Pb-exposed male brain exhibited increased <i>Taok3</i> expression (<i>p</i> < 0.05) and decreased DNA methylation (FDR < 0.01). The results demonstrate that perinatal Pb exposure stably influences longitudinal piRNA expression in a tissue- and sex-specific manner, potentially via DNA methylation-directed mechanisms.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2426952"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617066","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-10-04DOI: 10.1080/15592294.2024.2411470
Julian Hecker, Scott T Weiss, Jessica A Lasky-Su, Dawn L DeMeo, Christoph Lange
{"title":"Letter to the editor: critical evaluation of the reliability of DNA methylation probes on the illumina MethylationEPIC v1.0 BeadChip microarrays.","authors":"Julian Hecker, Scott T Weiss, Jessica A Lasky-Su, Dawn L DeMeo, Christoph Lange","doi":"10.1080/15592294.2024.2411470","DOIUrl":"10.1080/15592294.2024.2411470","url":null,"abstract":"","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2411470"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375193","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-12-08DOI: 10.1080/15592294.2024.2427999
Christopher R Beam, Kelly M Bakulski, Ebrahim Zandi, Eric Turkheimer, Morgan Lynch, Alaina I Gold, Thalida Em Arpawong, Sophie A Bell, Alyssa C Kam, Jonathan Becker, Deborah Winders Davis
{"title":"Epigenome-wide association study of loneliness in a sample of U.S. middle-aged twins.","authors":"Christopher R Beam, Kelly M Bakulski, Ebrahim Zandi, Eric Turkheimer, Morgan Lynch, Alaina I Gold, Thalida Em Arpawong, Sophie A Bell, Alyssa C Kam, Jonathan Becker, Deborah Winders Davis","doi":"10.1080/15592294.2024.2427999","DOIUrl":"10.1080/15592294.2024.2427999","url":null,"abstract":"<p><p>Loneliness is a complex human trait that is highly polygenic and found to affect gene expression related to inflammatory and immunological functioning. To date, no epigenome-wide association studies of loneliness have tested whether differentially methylated sites are annotated to genes associated with inflammatory and immunological processes. Using 281 individual adult twins' DNA methylation data from the Louisville Twin Study, we performed an epigenome-wide analysis of loneliness to address this gap in the literature. In the discovery analysis, 169 twins were used to prioritize probes and test associations with DNA methylation age acceleration, and 56 independent monozygotic (MZ) twin pairs (112 individuals) were used in a within-family replication analysis. Among the 837,274 sites analyzed, no probe sites were statistically significant at the genome-wide level (<i>p</i> < 5.97 × 10<sup>-8</sup>), but 25 suggestive sites (<i>p</i> < 5 × 10<sup>-5</sup>) were annotated to genes related to various biological processes, including inflammatory response and protein-binding functions that extend prior findings. The nominal associations at these suggestive probe sites were highly correlated (<i>r</i> = .72) between the discovery sample and the MZ pair replication sample. Finally, loneliness significantly correlated with the DunedinPACE DNA methylation measure, suggesting that higher levels of loneliness were associated with accelerated epigenetic age as quantified by a measure that indexes longitudinal changes across multiple organ systems.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2427999"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793911","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}