Epigenetics最新文献

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Epigenetic editing of BRCA1 promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells. BRCA1 启动子的表观遗传编辑增加了卵巢癌细胞对顺铂和奥拉帕尼的敏感性。
IF 3.7 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-05-26 DOI: 10.1080/15592294.2024.2357518
Wanhong He, Haijun Zhu, Sufen Zhang, Guang Shu, Han Lei, Maonan Wang, Gang Yin, Xiaohua Ni, Qihan Wu
{"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}
引用次数: 0
A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection. 用于胃癌检测的血浆无细胞 DNA 中两个甲基化 IRF4 片段和一个 ZEB2 片段的双基因面板。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-14 DOI: 10.1080/15592294.2024.2374988
Chunxiao Bu, Zhilong Wang, Xianping Lv, Yanteng Zhao
{"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<sup>-ΔΔCt</sup> 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}
引用次数: 0
TET1 displays catalytic and non-catalytic functions in the adult mouse cortex. TET1 在成年小鼠大脑皮层中具有催化和非催化功能。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-06 DOI: 10.1080/15592294.2024.2374979
Yee Hoon Foong, Blake Caldwell, Joanne L Thorvaldsen, Christopher Krapp, Clementina A Mesaros, Wanding Zhou, Rahul M Kohli, Marisa S Bartolomei
{"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}
引用次数: 0
Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA. 生长受限后代肾脏中的印迹基因改变可能是由长非编码 RNA 介导的。
IF 3.7 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2023-12-21 DOI: 10.1080/15592294.2023.2294516
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
{"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}
引用次数: 0
Genetic confounds of transgenerational epigenetic inheritance in mice. 小鼠跨代表观遗传的遗传混淆。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-02-18 DOI: 10.1080/15592294.2024.2318519
Daniel M Sapozhnikov, Moshe Szyf
{"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}
引用次数: 0
One-carbon metabolism nutrients impact the interplay between DNA methylation and gene expression in liver, enhancing protein synthesis in Atlantic salmon. 一碳代谢营养素影响肝脏中 DNA 甲基化与基因表达之间的相互作用,从而促进大西洋鲑鱼的蛋白质合成。
IF 3.7 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-02-25 DOI: 10.1080/15592294.2024.2318517
Takaya Saito, Marit Espe, Vibeke Vikeså, Christoph Bock, Tårn H Thomsen, Anne-Catrin Adam, Jorge M O Fernandes, Kaja H Skjaerven
{"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}
引用次数: 0
Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta. 5-hydroxymethylcytosine 的表观遗传学特征及其与胎盘中基因表达的关系。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-20 DOI: 10.1080/15592294.2024.2326869
Michael Mortillo, Elizabeth G Kennedy, Karen M Hermetz, Amber A Burt, Carmen J Marsit
{"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}
引用次数: 0
Comparative genomic analyses reveal evidence for adaptive A-to-I RNA editing in insect Adar gene. 比较基因组分析揭示了昆虫 Adar 基因中适应性 A 到 I RNA 编辑的证据。
IF 3.7 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI: 10.1080/15592294.2024.2333665
Caiqing Zheng, Ling Ma, Fan Song, Li Tian, Wanzhi Cai, Hu Li, Yuange Duan
{"title":"Comparative genomic analyses reveal evidence for adaptive A-to-I RNA editing in insect <i>Adar</i> gene.","authors":"Caiqing Zheng, Ling Ma, Fan Song, Li Tian, Wanzhi Cai, Hu Li, Yuange Duan","doi":"10.1080/15592294.2024.2333665","DOIUrl":"10.1080/15592294.2024.2333665","url":null,"abstract":"<p><p>Although A-to-I RNA editing leads to similar effects to A-to-G DNA mutation, nonsynonymous RNA editing (recoding) is believed to confer its adaptiveness by 'epigenetically' regulating proteomic diversity in a temporospatial manner, avoiding the pleiotropic effect of genomic mutations. Recent discoveries on the evolutionary trajectory of Ser>Gly auto-editing site in insect <i>Adar</i> gene demonstrated a selective advantage to having an editable codon compared to uneditable ones. However, apart from pure observations, quantitative approaches for justifying the adaptiveness of individual RNA editing sites are still lacking. We performed a comparative genomic analysis on 113 Diptera species, focusing on the <i>Adar</i> Ser>Gly auto-recoding site in <i>Drosophila</i>. We only found one species having a derived Gly at the corresponding site, and this occurrence was significantly lower than genome-wide random expectation. This suggests that the <i>Adar</i> Ser>Gly site is unlikely to be genomically replaced with G during evolution, and thus indicating the advantage of editable status over hardwired genomic alleles. Similar trends were observed for the conserved Ile>Met recoding in gene <i>Syt1</i>. In the light of evolution, we established a comparative genomic approach for quantitatively justifying the adaptiveness of individual editing sites. Priority should be given to such adaptive editing sites in future functional studies.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2333665"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206499","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}
引用次数: 0
GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis. GGNBP2 在精子发生过程中调控组蛋白泛素化和甲基化。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-07 DOI: 10.1080/15592294.2024.2381849
Kaimin Guo, Yin Cao, Zhiyi Zhao, Jiantao Zhao, Lingyun Liu, Hongliang Wang
{"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<sub>K119ubi</sub> and down-regulation of H2B<sub>K120ubi</sub> 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<sub>K27</sub> and H3<sub>K79</sub> 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<sub>K27</sub>trimethylation (H3<sub>K27me3</sub>) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3<sub>K79me2</sub>), 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}
引用次数: 0
Genomic context determines the effect of DNA methylation on gene expression in the gut epithelium of Atlantic salmon (Salmo salar). 基因组环境决定了 DNA 甲基化对大西洋鲑(Salmo salar)肠道上皮细胞基因表达的影响。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-16 DOI: 10.1080/15592294.2024.2392049
Aikaterini Katirtzoglou, Søren B Hansen, Harald Sveier, Michael D Martin, Jaelle C Brealey, Morten T Limborg
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