FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs
| العنوان: | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
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| المؤلفون: | Valentina Grossi, Giovanna Forte, Paola Sanese, Cristiano Simone, Vittoria Disciglio |
| المصدر: | Computational and Structural Biotechnology Journal, Vol 17, Iss, Pp 737-745 (2019) Computational and Structural Biotechnology Journal |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Aging, Review Article, Biochemistry, 0302 clinical medicine, FHRE, Forkhead response element, Structural Biology, PJS, Peutz-Jeghers syndrome, TAD, Topologically associated domain, media_common, SNP, Single nucleotide polymorphism, Genetics, 0303 health sciences, FOXO3, SOD2, Superoxide dismutase 2, Longevity, LD, Linkage disequilibrium, Phenotype, HSE, Heat shock element, ER, Estrogen receptor, Computer Science Applications, Chromatin, ACH, Active chromatin hub, 030220 oncology & carcinogenesis, FOXO3, Forkhead box 3, HPS, Hamartomatous polyposis syndrome, GPx, Glutathione peroxidase, SNV, Single nucleotide variant, GWAS, Genome-wide association study, Biotechnology, media_common.quotation_subject, lcsh:Biotechnology, Biophysics, SNP, Biology, 03 medical and health sciences, lcsh:TP248.13-248.65, Chromatin hub, Enhancer, Gene, Transcription factor, 030304 developmental biology, 5′UTR, Five prime untranslated region, 3C, Chromosome conformation capture, HSF1, Heat shock factor 1, Promoter, PHTS, PTEN hamartoma tumor syndrome, IGF-1, Insulin growth factor-1, ERE, Estrogen-responsive element, ROS, Reactive oxygen species |
| الوصف: | Health span is driven by a precise interplay between genes and the environment. Cell response to environmental cues is mediated by signaling cascades and genetic variants that affect gene expression by regulating chromatin plasticity. Indeed, they can promote the interaction of promoters with regulatory elements by forming active chromatin hubs. FOXO3 encodes a transcription factor with a strong impact on aging and age-related phenotypes, as it regulates stress response, therefore affecting lifespan. A significant association has been shown between human longevity and several FOXO3 variants located in intron 2. This haplotype block forms a putative aging chromatin hub in which FOXO3 has a central role, as it modulates the physical connection and activity of neighboring genes involved in age-related processes. Here we describe the role of FOXO3 and its single-nucleotide polymorphisms (SNPs) in healthy aging, with a focus on the enhancer region encompassing the SNP rs2802292, which upregulates FOXO3 expression and can promote the activity of the aging hub in response to different stress stimuli. FOXO3 protective effect on lifespan may be due to the accessibility of this region to transcription factors promoting its expression. This could in part explain the differences in FOXO3 association with longevity between genders, as its activity in females may be modulated by estrogens through estrogen receptor response elements located in the rs2802292-encompassing region. Altogether, the molecular mechanisms described here may help establish whether the rs2802292 SNP can be taken advantage of in predictive medicine and define the potential of targeting FOXO3 for age-related diseases. Graphical Abstract Unlabelled Image |
| اللغة: | English |
| تدمد: | 2001-0370 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::360c46f2a9feadbc0fa07938930830c6 http://www.sciencedirect.com/science/article/pii/S2001037019301011 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....360c46f2a9feadbc0fa07938930830c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20010370 |
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