Epigenetics最新文献_第8页

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":"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 H2AK119ubi and down-regulation of H2BK120ubi 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 H3K27 and H3K79 methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3K27trimethylation (H3K27me3) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3K79me2), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis.","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

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

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":"Supplementation of one-carbon (1C) metabolism micronutrients, which include B-vitamins and methionine, is essential for the healthy growth and development of Atlantic salmon (Salmo salar). 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.","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":"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 (p < 0.0001) at CpG islands (CGI), and enriched (p < 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 (p < 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 (p < 0.05 for both). Finally, we identified 107 differentially hydroxymethylated regions (DHMRs, p < 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.","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 Adar 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":"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 Adar 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 Adar Ser>Gly auto-recoding site in Drosophila. 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 Adar 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 Syt1. 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.","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

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

{"title":"Genomic context determines the effect of DNA methylation on gene expression in the gut epithelium of Atlantic salmon (Salmo salar).","authors":"Aikaterini Katirtzoglou, Søren B Hansen, Harald Sveier, Michael D Martin, Jaelle C Brealey, Morten T Limborg","doi":"10.1080/15592294.2024.2392049","DOIUrl":"10.1080/15592294.2024.2392049","url":null,"abstract":"The canonical view of DNA methylation, a pivotal epigenetic regulation mechanism in eukaryotes, dictates its role as a suppressor of gene activity, particularly within promoter regions. However, this view is being challenged as it is becoming increasingly evident that the connection between DNA methylation and gene expression varies depending on the genomic location and is therefore more complex than initially thought. We examined DNA methylation levels in the gut epithelium of Atlantic salmon (Salmo salar) using whole-genome bisulfite sequencing, which we correlated with gene expression data from RNA sequencing of the same gut tissue sample (RNA-seq). Assuming epigenetic signals might be pronounced between distinctive phenotypes, we compared large and small fish, finding 22 significant associations between 22 differentially methylated regions and 21 genes. We did not detect significant methylation differences between large and small fish. However, we observed a consistent signal of methylation levels around the transcription start sites (TSS), being negatively correlated with the expression levels of those genes. We found both negative and positive associations of methylation levels with gene expression further upstream or downstream of the TSS, revealing a more unpredictable pattern. The 21 genes showing significant methylation-expression correlations were involved in biological processes related to salmon health, such as growth and immune responses. Deciphering how DNA methylation affects the expression of such genes holds great potential for future applications. For instance, our results suggest the importance of genomic context in targeting epigenetic modifications to improve the welfare of aquaculture species like Atlantic salmon.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2392049"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992224","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

Expression patterns and clinical value of key m6A RNA modification regulators in smoking patients with coronary artery disease. 主要 m6A RNA 修饰调节因子在吸烟冠心病患者中的表达模式和临床价值。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-21 DOI: 10.1080/15592294.2024.2392400

Huanwei Zhuang, Hua Ouyang, Yangfei Peng, Shuji Gong, Kun Xiang, Le Chen, Jinlan Chen

{"title":"Expression patterns and clinical value of key m6A RNA modification regulators in smoking patients with coronary artery disease.","authors":"Huanwei Zhuang, Hua Ouyang, Yangfei Peng, Shuji Gong, Kun Xiang, Le Chen, Jinlan Chen","doi":"10.1080/15592294.2024.2392400","DOIUrl":"10.1080/15592294.2024.2392400","url":null,"abstract":"Even though N6-methyladenosine (m6A) RNA modifications are increasingly being implicated in human disease, their mechanisms are not fully understood in smokers with coronary artery disease (CAD). Thirty m6A-related regulators' expression (MRRE) in CAD individuals (smokers and non-smokers) were analyzed from GEO. Support Vector Machine, random forest, and nomogram models were constructed to assess its clinical value. Consensus clustering, principal component analysis, and ssGSEA were used to construct a full picture of m6A-related regulators in smokers with CAD. Oxygen-glucose deprivation (OGD) and qRT-PCR were used to validate hypoxia's effect on MRRE. A comparison between smokers with CAD and controls revealed lower expression levels of RBM15B, YTHDC2, and ZC3H13. Based on three key MRREs, all models showed good clinical value, and smokers with CAD were divided into two distinct molecular subgroups. The correlations were found between key MRRE and the degree of immune infiltration. Three key MRREs in HUVECs and FMC84 mouse cardiomyocytes were reduced in the OGD group. Through hypoxia, smoking might reduce the expression levels of RBM15B, YTHDC2, and ZC3H13 in smokers with CAD. Our findings provide an important theoretical basis for the treatment of smokers with CAD.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2392400"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016750","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

WGBS of embryonic gonads revealed that long non-coding RNAs in the MHM region might be involved in cell autonomous sex identity and female gonadal development in chickens. 胚胎性腺的WGBS表明，MHM区域的长链非编码rna可能参与了鸡细胞自主性别认同和雌性性腺发育。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2023-12-01 DOI: 10.1080/15592294.2023.2283657

Ligen Chen, Yu Cheng, Guixin Zhang, Yang Zhou, Zhen Zhang, Qianhong Chen, Yanping Feng

{"title":"WGBS of embryonic gonads revealed that long non-coding RNAs in the MHM region might be involved in cell autonomous sex identity and female gonadal development in chickens.","authors":"Ligen Chen, Yu Cheng, Guixin Zhang, Yang Zhou, Zhen Zhang, Qianhong Chen, Yanping Feng","doi":"10.1080/15592294.2023.2283657","DOIUrl":"10.1080/15592294.2023.2283657","url":null,"abstract":"DNA methylation plays a key role in sex determination and differentiation in vertebrates. However, there are few studies on DNA methylation involved in chicken gonad development, and most focused on male hypermethylated regions (MHM). It is unclear whether there are specific differentially methylated regions (DMRs) in chicken embryonic gonads regulating sex determination and differentiation. Here, the DNA methylation maps showed that the difference of DNA methylation level between sexes was much higher at embryonic day 10 (E10) than that at embryonic day 6 (E6), and the significant differentially methylated regions at both stages were mainly distributed on the Z chromosome, including MHM1 and MHM2. The results of bisulphite sequencing PCR (BSP) and qRT-PCR showed hypomethylation of female MHM and upregulation of long non-coding RNAs (lncRNAs) whose promoter in the MHM region was consistent with the sequencing results, and similar results were in brain and muscle. In female sex-reversed gonads, the methylation pattern of MHM remained unchanged, and the expression levels of the three candidate lncRNAs were significantly decreased compared with those in females, but were significantly increased compared to males. The fluorescence in situ hybridization (FISH) results also showed that these lncRNAs were highly expressed in female embryonic gonads. The results of methyltransferase inhibitor and dual-luciferase reporter assay suggest that lncRNA expression may be regulated by DNA methylation within their promoters. Therefore, we speculated that MHM may be involved in cell-autonomous sex identity in chickens, and that lncRNAs regulated by MHM may be involved in female sexual differentiation.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2283657"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458648","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

Generational stability of epigenetic transgenerational inheritance facilitates adaptation and evolution. 表观遗传的世代稳定性有利于适应和进化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-05 DOI: 10.1080/15592294.2024.2380929

Alexandra Korolenko, Michael K Skinner

{"title":"Generational stability of epigenetic transgenerational inheritance facilitates adaptation and evolution.","authors":"Alexandra Korolenko, Michael K Skinner","doi":"10.1080/15592294.2024.2380929","DOIUrl":"10.1080/15592294.2024.2380929","url":null,"abstract":"The epigenome and epigenetic inheritance were not included in the original modern synthesis theory or more recent extended evolutionary synthesis of evolution. In a broad range of species, the environment has been shown to play a significant role in natural selection, which more recently has been shown to occur through epigenetic alterations and epigenetic inheritance. However, even with this evidence, the field of epigenetics and epigenetic inheritance has been left out of modern evolutionary synthesis, as well as other current evolutionary models. Epigenetic mechanisms can direct the regulation of genetic processes (e.g. gene expression) and also can be directly changed by the environment. In contrast, DNA sequence cannot be directly altered by the environment. The goal of this review is to present the evidence of how epigenetics and epigenetic inheritance can alter phenotypic variation in numerous species. This can occur at a significantly higher frequency than genetic change, so correlates with the frequency of evolutionary change. In addition, the concept and importance of generational stability of transgenerational inheritance is incorporated into evolutionary theory. For there to be a better understanding of evolutionary biology, we must incorporate all aspects of molecular (e.g. genetics and epigenetics) and biological sciences (e.g. environment and adaptation).","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2380929"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893150","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 architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in CD46 and other loci. 老年人脑组织表观遗传皮层时钟年龄的遗传结构：CD46 和其他位点的改变。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-22 DOI: 10.1080/15592294.2024.2392050

Francine Grodstein, Bernardo Lemos, Jingyun Yang, Katia de Paiva Lopes, Ricardo A Vialle, Nicholas Seyfried, Yanling Wang, Gemma Shireby, Eilis Hannon, Alan Thomas, Keeley Brookes, Jonathan Mill, Philip L De Jager, David A Bennett

{"title":"Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in CD46 and other loci.","authors":"Francine Grodstein, Bernardo Lemos, Jingyun Yang, Katia de Paiva Lopes, Ricardo A Vialle, Nicholas Seyfried, Yanling Wang, Gemma Shireby, Eilis Hannon, Alan Thomas, Keeley Brookes, Jonathan Mill, Philip L De Jager, David A Bennett","doi":"10.1080/15592294.2024.2392050","DOIUrl":"10.1080/15592294.2024.2392050","url":null,"abstract":"The cortical epigenetic clock was developed in brain tissue as a biomarker of brain aging. As one way to identify mechanisms underlying aging, we conducted a GWAS of cortical age. We leveraged postmortem cortex tissue and genotyping array data from 694 participants of the Rush Memory and Aging Project and Religious Orders Study (ROSMAP; 11000,000 SNPs), and meta-analysed ROSMAP with 522 participants of Brains for Dementia Research (5,000,000 overlapping SNPs). We confirmed results using eQTL (cortical bulk and single nucleus gene expression), cortical protein levels (ROSMAP), and phenome-wide association studies (clinical/neuropathologic phenotypes, ROSMAP). In the meta-analysis, the strongest association was rs4244620 (p = 1.29 × 10-7), which also exhibited FDR-significant cis-eQTL effects for CD46 in bulk and single nucleus (microglia, astrocyte, oligodendrocyte, neuron) cortical gene expression. Additionally, rs4244620 was nominally associated with lower cognition, faster slopes of cognitive decline, and greater Parkinsonian signs (n ~ 1700 ROSMAP with SNP/phenotypic data; all p ≤ 0.04). In ROSMAP alone, the top SNP was rs4721030 (p = 8.64 × 10-8) annotated to TMEM106B and THSD7A. Further, in ROSMAP (n = 849), TMEM106B and THSD7A protein levels in cortex were related to many phenotypes, including greater AD pathology and lower cognition (all p ≤ 0.0007). Overall, we identified converging evidence of CD46 and possibly TMEM106B/THSD7A for potential roles in cortical epigenetic clock age.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2392050"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016751","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