Search results for "CpG island"
showing 10 items of 66 documents
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
2021
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…
Metilazione del DNA in artrite reumatoide
2005
Lo stato di metilazione del DNA genomico e del gene PTHrP è stato valutato con tecniche molecolari e citogenetiche in artrite reumatoide (AR), patologia autoimmune caratterizzata anche da alta incidenza di linfomi e da ipercalcemia per overespressione del gene PTHrP. La metilazione del DNA, infatti, ha un ruolo critico nello sviluppo delle malattie neoplastiche; il gene PTHrP avendo tre promotori uno dei quali contiene un’isola CpG è un buon candidato per la deregolazione da alterato pattern di metilazione locale. Le indagini sulla metilazione genomica, condotte su DNA estratto da sangue periferico di pazienti e di donatori e amplificato in reazioni di Methylation-Sensitive Arbitrarily Prim…
Somatic mutation profiles as molecular classifiers of ulcerative colitis-associated colorectal cancer.
2021
Ulcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question by determining the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). The findings were compared to Lynch syndrome (LS), a different form of cancer predisposition that shares the importance of immunological factors in tumorigenesis. CA-CRCs (n=27) were investigated for microsatellite instability, CpG island methylator phenotype, and somatic mutations of 999 cancer-relevant genes ("Pan-cancer" panel). A subpanel of "Pan-cancer" design (578 genes) was used for LS colorectal tumors (n=28). Mutational loads and signatures stratifie…
PTHrP in differentiating human mesenchymal stem cells: Transcript isoform expression, promoter methylation, and protein accumulation
2013
Human PTHrP gene displays a complex organization with nine exons producing diverse mRNA variants due to alternative splicing at 5' and 3' ends and the existence of three different transcriptional promoters (P1, P2 and P3), two of which (P2 and P3) contain CpG islands. It is known that the expression of PTHrP isoforms may be differentially regulated in a developmental stage- and tissue-specific manner. To search for novel molecular markers of stemness/differentiation, here we have examined isoform expression in fat-derived mesenchymal stem cells both maintained in stem conditions and induced toward adipo- and osteogenesis. In addition, the expression of the splicing isoforms derived from P2 …
Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers
2015
Abstract Analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed regional DNA hypermethylation embedded in extensive global hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM as compared to normal plasma cells were located outside CpG islands and were unexpectedly associated with intronic enhancer regions active in normal B cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with downregulation of its host genes. ChIP-seq and DNAseI-se…
Methyl-CpG-binding proteins
2000
CpG methylation, the most common epigenetic modification of vertebrate genomes, is primarily associated with transcriptional repression. MeCP2, MBD1, MBD2, MBD3 and MBD4 constitute a family of vertebrate proteins that share the methyl-CpG-binding domain (MBD). The MBD, consisting of about 70 residues, possesses a unique alpha/beta-sandwich structure with characteristic loops, and is able to bind single methylated CpG pairs as a monomer. All MBDs except MBD4, an endonuclease that forms a complex with the DNA mismatch-repair protein MLH1, form complexes with histone deacetylase. It has been established that MeCP2, MBD1 and MBD2 are involved in histone deacetylase-dependent repression and it i…
Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity
2014
AbstractThe combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which wa…
Activation and selective IL-17 response of human Vγ9Vδ2 T lymphocytes by TLR-activated plasmacytoid dendritic cells.
2016
// Elena Lo Presti 1,2 , Nadia Caccamo 1,2 , Valentina Orlando 1,2 , Francesco Dieli 1,2 and Serena Meraviglia 1,2 1 Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy 2 Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy Correspondence to: Serena Meraviglia, email: // Keywords : γδ T cells, plasmacytoid dendritic cells, IL-17, TLR activation, proliferation, Immunology and Microbiology Section, Immune response, Immunity Received : July 20, 2016 Accepted : August 02, 2016 Published :August 31, 2016 Abstract Vγ9Vδ2 T cells and plasmacytoid dendritic cells (pDCs) are two distinc…
Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1)
2001
Human chromosome 11p15.3 is associated with chromosome aberrations in the Beckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor types including lung cancer and leukemias. To date, only single tumor-relevant genes with linkage to this region (e.g. LMO1) have been found suggesting that this region may harbor additional potential disease associated genes. Although this genomic area has been studied for years, the exact order of genes/chromosome markers between D11S572 and the WEE1 gene locus remained unclear. Using the FISH technique and PAC clones of the flanking markers we determined the order of the genomic markers. Based on these clones we established a PAC cont…
Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation?
2012
Background: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. Aim: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. Results: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enz…