Epigenetics最新文献_第7页

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":null,"pages":null},"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

Epigenetic changes in pyloric caeca of Atlantic salmon fed diets containing increasing levels of lipids and choline. 大西洋鲑幽门盲肠的表观遗传学变化，喂食含脂量和胆碱量不断增加的食物。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-01-28 DOI: 10.1080/15592294.2024.2305079

Anusha K S Dhanasiri, Daphne Siciliani, Trond M Kortner, Åshild Krogdahl

{"title":"Epigenetic changes in pyloric caeca of Atlantic salmon fed diets containing increasing levels of lipids and choline.","authors":"Anusha K S Dhanasiri, Daphne Siciliani, Trond M Kortner, Åshild Krogdahl","doi":"10.1080/15592294.2024.2305079","DOIUrl":"10.1080/15592294.2024.2305079","url":null,"abstract":"An earlier study of ours investigating the effect of dietary lipid levels on the choline requirement of Atlantic salmon showed increasing severity of intestinal steatosis with increasing lipid levels. As choline is involved in epigenetic regulation by being the key methyl donor, pyloric caeca samples from the study were analysed for epigenetic effects of dietary lipid and choline levels. The diets varied in lipid levels between 16% and 28%, and choline levels between 1.9 and 2.3 g/kg. The diets were fed for 8 weeks to Atlantic salmon of 25 g of initial weight. Using reduced representation bisulfite sequencing (RRBS), this study revealed that increasing dietary lipid levels induced methylation differences in genes involved in membrane transport and signalling pathways, and in microRNAs important for the regulation of lipid homoeostasis. Increasing choline levels also affected genes involved in fatty acid biosynthesis and transport, lipolysis, and lipogenesis, as well as important immune genes. Our observations confirmed that choline is involved in epigenetic regulation in Atlantic salmon, as has been reported for higher vertebrates. This study showed the need for the inclusion of biomarkers of epigenetic processes in studies that must be conducted to define optimal choline levels in diets for Atlantic salmon.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569951","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

Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida. 孟加拉脊柱裂婴儿的父母砷暴露和组织特异性 DNA 甲基化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-19 DOI: 10.1080/15592294.2024.2416345

Gwen Tindula, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D M Arman, Joynul Islam, Subrata Kumar Biswas, Benjamin C Warf, David C Christiani, Bernardo Lemos, Liming Liang, Andres Cardenas, Maitreyi Mazumdar

{"title":"Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida.","authors":"Gwen Tindula, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D M Arman, Joynul Islam, Subrata Kumar Biswas, Benjamin C Warf, David C Christiani, Bernardo Lemos, Liming Liang, Andres Cardenas, Maitreyi Mazumdar","doi":"10.1080/15592294.2024.2416345","DOIUrl":"10.1080/15592294.2024.2416345","url":null,"abstract":"An emerging hypothesis linking arsenic toxicity involves altered epigenetic mechanisms, such as DNA methylation. In this study, we examined the relationship between parents' arsenic exposure and DNA methylation in tissues obtained from 28 infants with spina bifida from Bangladesh. We analyzed arsenic in parents' toenails using inductively coupled plasma mass spectrometry (ICP-MS). DNA methylation was measured in infants' dural tissue, buccal swabs, and whole blood using the Illumina Infinium MethylationEPIC BeadChip. We performed epigenome-wide association analyses (EWAS) and tested differentially methylated regions (DMRs). In EWAS, DNA methylation at cg24039697 in dural tissue was positively associated (β = 0.59, p = 7.6 × 10-9) with father's toenail arsenic concentrations, adjusting for covariates. We did not identify any CpG sites related to father's arsenic exposure in the other tissues, or any CpG sites related to mother's arsenic exposure. Gene ontology analysis identified many biological pathways of interest, including the Wnt signaling pathways. We identified several DMRs across the tissues related to arsenic exposure that included probes mapping to genes that have previously been identified in studies of neural tube defects. This study emphasizes the potential impact of arsenic exposure in fathers, often understudied in epidemiological studies, on DNA methylation in a unique neurological tissue specific to spina bifida.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460921","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

DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer. 局部前列腺癌男性队列中转移风险的 DNA 甲基化标记。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI: 10.1080/15592294.2024.2308920

Talar S Habeshian, Kimberly L Cannavale, Jeff M Slezak, Yu-Hsiang Shu, Gary W Chien, XuFeng Chen, Feng Shi, Kimberly D Siegmund, Stephen K Van Den Eeden, Jiaoti Huang, Chun R Chao

{"title":"DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer.","authors":"Talar S Habeshian, Kimberly L Cannavale, Jeff M Slezak, Yu-Hsiang Shu, Gary W Chien, XuFeng Chen, Feng Shi, Kimberly D Siegmund, Stephen K Van Den Eeden, Jiaoti Huang, Chun R Chao","doi":"10.1080/15592294.2024.2308920","DOIUrl":"10.1080/15592294.2024.2308920","url":null,"abstract":"Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206525","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

Widespread genomic de novo DNA methylation occurs following CD8⁺ T cell activation and proliferation. CD8+ T 细胞活化和增殖后，基因组会发生广泛的新 DNA 甲基化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1080/15592294.2024.2367385

Annika R Seddon, Olivia M Damiano, Mark B Hampton, Aaron J Stevens

{"title":"Widespread genomic de novo DNA methylation occurs following CD8+ T cell activation and proliferation.","authors":"Annika R Seddon, Olivia M Damiano, Mark B Hampton, Aaron J Stevens","doi":"10.1080/15592294.2024.2367385","DOIUrl":"10.1080/15592294.2024.2367385","url":null,"abstract":"This research investigates the intricate dynamics of DNA methylation in the hours following CD8+ T cell activation, during a critical yet understudied temporal window. DNA methylation is an epigenetic modification central to regulation of gene expression and directing immune responses. Our investigation spanned 96-h post-activation and unveils a nuanced tapestry of global and site-specific methylation changes. We identified 15,626 significant differentially methylated CpGs spread across the genome, with the most significant changes occurring within the genes ADAM10, ICA1, and LAPTM5. While many changes had modest effect sizes, approximately 120 CpGs exhibited a log2FC above 1.5, with cell activation and proliferation pathways the most affected. Relatively few of the differentially methylated CpGs occurred along adjacent gene regions. The exceptions were seven differentially methylated gene regions, with the Human T cell Receptor Alpha Joining Genes demonstrating consistent methylation change over a 3kb window. We also investigated whether an inflammatory environment could alter DNA methylation during activation, with proliferating cells exposed to the oxidant glycine chloramine. No substantial differential methylation was observed in this context. The temporal perspective of early activation adds depth to the evolving field of epigenetic immunology, offering insights with implications for therapeutic innovation and expanding our understanding of epigenetic modulation in immune function.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426552","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

Correction. 更正。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-04 DOI: 10.1080/15592294.2024.2388007

引用次数: 0

Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome. 利用 Methyl-Seq 平台鉴定大鼠表观基因组中组织和性别特异性 DNA 甲基化差异。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-09-22 DOI: 10.1080/15592294.2024.2393945

Olivia H Cox, Fayaz Seifuddin, Jeffrey Guo, Mehdi Pirooznia, Gretha J Boersma, Josh Wang, Kellie L K Tamashiro, Richard S Lee

{"title":"Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome.","authors":"Olivia H Cox, Fayaz Seifuddin, Jeffrey Guo, Mehdi Pirooznia, Gretha J Boersma, Josh Wang, Kellie L K Tamashiro, Richard S Lee","doi":"10.1080/15592294.2024.2393945","DOIUrl":"10.1080/15592294.2024.2393945","url":null,"abstract":"Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat's immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes. In this study, we implemented the rat Methyl-Seq platform and tested its ability to distinguish differentially methylated regions (DMRs) among three different tissue types, three distinct brain regions, and, in the hippocampus, between males and females. These comparisons yielded DNAm differences of differing magnitudes, many of which were independently validated by bisulfite pyrosequencing, including autosomal regions that were predicted to show the least degree of difference in DNAm between males and females. Quantitative reverse transcription PCR revealed that most genes associated with the DMRs showed tissue-, brain region-, and sex-specific differences in expression. In particular, we found evidence for sex-specific DNAm and expression differences at Tubb6, Lrrn2, Tex26, and Sox5l1, all of which play important roles in neurodevelopment and have been implicated in studies examining sex differences. Our results demonstrate the utility of the rat Methyl-Seq platform and suggest the presence of DNAm differences between the male and female hippocampus. The rat Methyl-Seq has the potential to provide epigenomic insights into pharmacological and behavioral studies performed in the rat.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282290","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

Biogenesis of circRBM33 mediated by N6-methyladenosine and its function in abdominal aortic aneurysm. 由 N6-甲基腺苷介导的 circRBM33 的生物生成及其在腹主动脉瘤中的功能。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/15592294.2024.2392401

Yingqi Xu, Xiang Weng, Jiacong Qiu, Shizhi Wang

{"title":"Biogenesis of circRBM33 mediated by N6-methyladenosine and its function in abdominal aortic aneurysm.","authors":"Yingqi Xu, Xiang Weng, Jiacong Qiu, Shizhi Wang","doi":"10.1080/15592294.2024.2392401","DOIUrl":"10.1080/15592294.2024.2392401","url":null,"abstract":"This study aimed to explore whether m6A modification affects the biogenesis of circRBM33, which is involved in the progression of abdominal aortic aneurysm (AAA). For in vitro experiments, vascular smooth muscle cells (VSMCs) were treated with Ang II. MeRIP‒PCR was used to assess m6A modification of circRBM33. Gene expression was measured using RT‒qPCR and Western blotting. For in vivo experiments, a mouse model of AAA was established via Ang II infusion. HE, Sirius Red and TUNEL staining was performed to evaluate pathological changes and cell apoptosis in aortic vessels. The results showed that the m6A level of circRBM33 was abnormally increased in Ang II-induced VSMCs. In addition, METTL3 positively regulated circRBM33 expression. YTHDC1 deficiency decreased circRBM33 expression but had no effect on RBM33 mRNA expression. Notably, neither METTL3 nor YTHDC1 influenced the stability of circRBM33 or RBM33 mRNA. The interaction between circRBM33 and METTL3/YTHDC1 was verified by RIP analysis. Moreover, the Ang II-induced increase in circRBM33 expression was reversed by cycloleucine (an inhibitor of m6A methylation). Importantly, the m6A modification and expression of circRBM33 in the circRBM33-m6A-mut2-expressing VSMCs were not altered by METTL3 silencing. Mechanistically, METTL3/YTHDC1 modulates the biogenesis of circRBM33 in an m6A-dependent manner. In addition, circRBM33 knockdown alleviated AAA by reducing ECM degradation in the Ang II-infused mice. In conclusion, this study demonstrated that METTL3/YTHDC1-mediated m6A modification modulates the biogenesis of circRBM33 from exons of the RBM33 gene. Moreover, knockdown of circRBM33 alleviated AAA by reducing ECM degradation, which may provide a novel therapeutic strategy for treating AAA.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153399","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

Maternal glucose levels and late pregnancy circulating extracellular vesicle and particle miRNAs in the MADRES pregnancy cohort. MADRES 妊娠队列中的母体血糖水平与妊娠晚期循环细胞外囊泡和颗粒 miRNAs。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-09-18 DOI: 10.1080/15592294.2024.2404198

Elizabeth C Anderson,Helen B Foley,Joshua J Levy,Megan E Romano,Jiang Gui,Jessica L Bentz,Luis E Maldonado,Shohreh F Farzan,Theresa M Bastain,Carmen J Marsit,Carrie V Breton,Caitlin G Howe

引用次数: 0

Exploring fatty acids from royal jelly as a source of histone deacetylase inhibitors: from the hive to applications in human well-being and health. 探索从蜂王浆中提取脂肪酸作为组蛋白去乙酰化酶抑制剂的来源：从蜂巢到在人类福祉和健康中的应用。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-09-10 DOI: 10.1080/15592294.2024.2400423

Fernanda Aparecida Dos Santos France,Debora Kazumi Maeda,Ana Beatriz Rodrigues,Mai Ono,Franciele Lopes Nogueira Marchetti,Marcos Martins Marchetti,Allana Cristina Faustino Martins,Roberto da Silva Gomes,Cláudia Aparecida Rainho

{"title":"Exploring fatty acids from royal jelly as a source of histone deacetylase inhibitors: from the hive to applications in human well-being and health.","authors":"Fernanda Aparecida Dos Santos France,Debora Kazumi Maeda,Ana Beatriz Rodrigues,Mai Ono,Franciele Lopes Nogueira Marchetti,Marcos Martins Marchetti,Allana Cristina Faustino Martins,Roberto da Silva Gomes,Cláudia Aparecida Rainho","doi":"10.1080/15592294.2024.2400423","DOIUrl":"https://doi.org/10.1080/15592294.2024.2400423","url":null,"abstract":"A differential diet with royal jelly (RJ) during early larval development in honeybees shapes the phenotype, which is probably mediated by epigenetic regulation of gene expression. Evidence indicates that small molecules in RJ can modulate gene expression in mammalian cells, such as the fatty acid 10-hydroxy-2-decenoic acid (10-HDA), previously associated with the inhibition of histone deacetylase enzymes (HDACs). Therefore, we combined computational (molecular docking simulations) and experimental approaches for the screening of potential HDAC inhibitors (HDACi) among 32 RJ-derived fatty acids. Biochemical assays and gene expression analyses (Reverse Transcriptase - quantitative Polymerase Chain Reaction) were performed to evaluate the functional effects of the major RJ fatty acids, 10-HDA and 10-HDAA (10-hydroxy-decanoic acid), in two human cancer cell lines (HCT116 and MDA-MB-231). The molecular docking simulations indicate that these fatty acids might interact with class I HDACs, specifically with the catalytic domain of human HDAC2, likewise well-known HDAC inhibitors (HDACi) such as SAHA (suberoylanilide hydroxamic acid) and TSA (Trichostatin A). In addition, the combined treatment with 10-HDA and 10-HDAA inhibits the activity of human nuclear HDACs and leads to a slight increase in the expression of HDAC-coding genes in cancer cells. Our findings indicate that royal jelly fatty acids collectively contribute to HDAC inhibition and that 10-HDA and 10-HDAA are weak HDACi that facilitate the acetylation of lysine residues of chromatin, triggering an increase in gene expression levels in cancer cells.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0