- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- Ferroptosis and cancer prognosis
- Birth, Development, and Health
- Mesenchymal stem cell research
- Diet and metabolism studies
- Genetics, Aging, and Longevity in Model Organisms
- High Altitude and Hypoxia
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- Cancer Research and Treatments
- MicroRNA in disease regulation
- Autism Spectrum Disorder Research
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Glioma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Metabolism and Genetic Disorders
Nanomaterials and Nanotechnology Research Center
2017-2024
Universidad de Oviedo
2014-2024
Centre for Biomedical Network Research on Rare Diseases
2021-2024
Research Network (United States)
2024
Consejo Superior de Investigaciones Científicas
2011-2024
Instituto de Investigación Sanitaria del Principado de Asturias
2012-2023
Centro de Investigación Biomédica en Red
2023
Gobierno del Principado de Asturias
2023
Instituto de Salud Carlos III
2021
Central University Hospital of Asturias
2019
DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis drug response. With suitable assays after validation large cohorts, associations can be exploited for clinical diagnostics personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing performance all widely used methods analysis that compatible routine use. We shipped 32 reference samples to...
The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem in a process known as reprogramming. Notably, partial reversible reprogramming does not change cell identity but reverse markers aging cells, improve capacity aged mice to repair tissue injuries, extend longevity progeroid mice. However, little is about mechanisms involved. Here, we have studied changes DNA methylome, transcriptome, metabolome naturally...
Are there DNA methylation alterations in sperm that could explain the reduced biological fertility of male partners from couples with unexplained infertility? patterns, not only at specific loci but also Alu Yb8 repetitive sequences, are altered infertile individuals compared fertile controls. Aberrant has been associated human infertility patients demonstrating either deficiencies process spermatogenesis or low semen quality. Case and control prospective study. This study compares 46...
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate post-transcriptional gene expression. They influence a wide range of physiological functions, including neuronal processes, and regulated by various mechanisms, such as DNA methylation. This epigenetic mark is recognized transcriptional regulators the methyl CpG binding protein Mecp2. Rett syndrome complex neurological disorder has been associated with mutations in coding for Thus, we examined possible miRNA misregulation...
The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation major regulator transcriptional activity, aberrations in the distribution this epigenetic mark may be involved many neurological disorders, such as Alzheimer's disease. Herein, we have analysed 12 distinct mouse brain regions according their CpG 5'-end patterns observed unique landscapes. methylomes obtained from cerebral cortex were used...
In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks changes methylation adult stem cells during lifetime are still largely unknown. Here, profiling mesenchymal (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites aging. As sequences were marks. Most importantly, strongly active mark H3K4me1 suggesting...
The purpose of this study was to determine the global patterns aberrant DNA methylation in thyroid cancer.We have used arrays determine, for first time, genome-wide promoter status papillary, follicular, medullary, and anaplastic tumors.We identified 262 352 hypermethylated 13 21 hypomethylated genes differentiated papillary follicular tumors, respectively. Interestingly, other tumor types analyzed displayed more (280 393 medullary tumors) than aberrantly (86 131 tumors). Among indentified,...
Rett syndrome (RTT) is a complex neurological disorder that one of the most frequent causes mental retardation in women. A great landmark research this field was discovery relationship between disease and presence mutations gene codes for methyl-CpG binding protein 2 (MeCP2). Currently, MeCP2 thought to act as transcriptional repressor couples DNA methylation silencing. The present study aimed identify new target genes regulated by Mecp2 mouse model RTT.We have compared expression profiles...
Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood. Here, we show that promoter DNA demethylation is associated with activation of hematopoietic-specific genes. Using genome-wide methylation arrays, identified 694 genes repressed by in human embryonic stem cells and whose loss hematopoietic can be expression. The association between was studied many including CD45, CD34, CD28, CD19, T cell receptor (TCR), MHC class II HLA-DR,...
Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematologic compartment that may enhance antitumor immune responses, mainly by activation of dendritic cells. Here, we show more than one-third human colorectal tumors exhibit aberrant DNA demethylation GM-CSF promoter and overexpress cytokine. Mouse engraftment experiments with autologous homologous colon engineered to repress ectopic secretion revealed tumor-secreted have an immune-associated...
Early life is a period of drastic epigenetic remodeling in which the epigenome especially sensitive to extrinsic and intrinsic influence. However, epigenome-wide dynamics DNA methylation changes that occur during this have not been sufficiently characterized longitudinal studies.To end, we studied status more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth 5 10 years age, then chromatin context associated with these loci by...
Loss of 5-hydroxymethylcytosine (5hmC) has been associated with mutations the ten-eleven translocation (TET) enzymes in several types cancer. However, tumors wild-type TET genes can also display low 5hmC levels, suggesting that other mechanisms involved gene regulation might be implicated decline this epigenetic mark. Here we show DNA hypermethylation and loss hydroxymethylation, as well a marked reduction activating histone marks TET3 gene, impair expression lead to genome-wide levels...
Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance epigenetic changes cancer immunology prompted us to determine impact DNA methylation profiles on course.We recruited 114 patients with comprising 77 acute lymphoblastic leukemia and 37 non-Hodgkin lymphoma who were treated cells. Using a comprehensive...
Abstract Aging involves the deterioration of organismal function, leading to emergence multiple pathologies. Environmental stimuli, including lifestyle, can influence trajectory this process and may be used as tools in pursuit healthy aging. To evaluate role epigenetic mechanisms context, we have generated bulk tissue single cell multi-omic maps male mouse dorsal hippocampus young old animals exposed environmental stimulation form enriched environments. We present a molecular atlas aging...
Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one the earliest manifestations alcohol-induced injury, restoring activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as mediator ALD progression hypothesize that targeting MCJ may help recovering fitness without collateral damage....
The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that of DNMT3b post-transcriptionally regulated by HuR, an RNA-binding protein stabilizes and/or modulates translation target mRNAs. presence a putative HuR-recognition motif 3′UTR prompted studies investigate if this transcript...
Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them still largely unknown. The present study aimed determine possible role certain epigenetic in cellular response human lung epithelial cells that triggered by long-term exposure titanium dioxide (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). results showed TiO2NPs had only minor on genome-wide DNA methylation. However, we...
Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role process. Here, we analyzed genome-wide profile 5hmc mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2–89 years. We identified 10,685 frequently hydroxymethylated CpG sites MSCs were, as other cell types, significantly associated with low density...
// María G. García 1, 2 , Antonella Carella Rocío Urdinguio Gustavo F. Bayón 1 Virginia Lopez Juan Ramón Tejedor 3 Marta I. Sierra Estela García-Toraño Pablo Santamarina Raúl Perez Cristina Mangas Aurora Astudillo 4 M. Daniela Corte-Torres 5 Inés Sáenz-de-Santa-María 6 María-Dolores Chiara Agustín Fernández and Mario Fraga Institute of Oncology Asturias (IUOPA), HUCA, Universidad de Oviedo,...
Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was identification and characterization CpG sites that are modified with time We hypothesize these changes would lead detection genes might be epigenetically modulated by environmental factors early childhood which, if disturbed, contribute susceptibility diseases later in The study pattern 485577 performed on 30...
Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study possible role 5-hydroxymethylcytosine (5hmC) in this process we analyzed global and locus-specific genome-wide levels 5hmC 5-methylcytosine (5mC) human primary samples from 12 non-tumoral brains 53 gliomas. We found that identified were significantly reduced Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant strongly...