Search results for "Epigenomics"

DNA combinatorial messages and Epigenomics: The case of chromatin organization and nucleosome occupancy in eukaryotic genomes

2019

Abstract Epigenomics is the study of modifications on the genetic material of a cell that do not depend on changes in the DNA sequence, since those latter involve specific proteins around which DNA wraps. The end result is that Epigenomic changes have a fundamental role in the proper working of each cell in Eukaryotic organisms. A particularly important part of Epigenomics concentrates on the study of chromatin, that is, a fiber composed of a DNA-protein complex and very characterizing of Eukaryotes. Understanding how chromatin is assembled and how it changes is fundamental for Biology. In more than thirty years of research in this area, Mathematics and Theoretical Computer Science have gai…

EPIGENOMICS AND METABOLOMICS MECHANISMS FOR A GENE X DIET INTERACTION MODULATING AGE-RELATED OBESITY

2018

A functional variant in the apolipoprotein AII (APOA2) gene (rs5082) predisposes homozygous carriers to age-related obesity when habitual saturated fat (SFA) intake is high. We used epigenomics, transcription and metabolomics analyses to identify currently unknown mechanisms underlying this well-replicated gene x diet interaction. We conducted an epigenome-wide scan to compare genetically at-risk to low-risk individuals with low (<22 g/d) or high (≥22 g/d) SFA intake in the Boston Puerto Rican Health Study and validated the findings in the GOLDN Study and the Framingham Heart Study. In these three populations, we identified genotype-dependent differential methylation, only with high SFA int…

Developmental and Early Life Origins of Cardiometabolic Risk Factors

2021

The intent of this review is to critically consider the data that support the concept of programming and its implications. Birth weight and growth trajectories during childhood are associated with cardiometabolic disease in adult life. Both extremes, low and high birth weight coupled with postnatal growth increase the early presence of cardiometabolic risk factors and vascular imprinting, crucial elements of this framework. Data coming from epigenetics, proteomics, metabolomics, and microbiota added relevant information and contribute to better understanding of mechanisms as well as development of biomarkers helping to move forward to take actions. Research has reached a stage in which suff…

DNA methylation patterns in newborns exposed to tobacco in utero

2015

[Background] Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.

A motif-independent metric for DNA sequence specificity

2011

Abstract Background Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity. Results We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM). By analyzing both simulated and real experimental data, we found that the MIM measure can be used to detect sequence specificity independent of presence of transcription factor (TF) binding motifs. We…

DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific.

2000

Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet). In mammals MAT activity derives from two separate genes which display a tissue-specific pattern of expression. While MAT1A is expressed only in the adult liver, MAT2A is expressed in non-hepatic tissues. The mechanisms behind the selective expression of these two genes are not fully understood. In the present report we have evaluated MAT1A and MAT2A methylation in liver and in other tissues, such as kidney, by methylation-sensitive restriction enzyme digestion of genomic DNA. Our data indicate that MAT1A is hypomethylated in liver and hypermethylated in non-expressing tissues. The opposite situ…

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…

Epigenomics in acute cerebrovascular diseases.

2020

Abstract LB-099: Metabolic vulnerabilities of mesenchymal-like EGFR-mutant NSCLC cells with acquired resistance to tyrosine kinase inhibitors

2018

Abstract Despite the availability of the effective targeted therapies in lung cancer, such as EGFR tyrosine kinase inhibitors (TKIs), drug tolerance and acquired resistance are two common problems that negatively impact lung cancer patient survival. Consequently it is important to understand the molecular basis of the drug tolerance and resistance so that we could formulate effective strategies to ameliorate the efficacy of existing drug and to suppress the emergence of drug resistance. A burgeoning body of literature demonstrated that epigenetic changes by the methylation of DNA and histones are critical in acquired drug resistance, especially in those cancer cells with stem cell-like prop…

EPCT-15. RAPID EPIGENOMIC CLASSIFICATION OF BRAIN TUMORS ENABLES INTRAOPERATIVE NEUROSURGICAL RISK MODULATION

2021

Abstract Background Clear identification of tumor subtype is the main predictor of patient outcome and ultimately what is considered an adequate level of surgical risk. At brain tumor resection, imaging modalities and intraoperative histology often give an ambigious diagnosis, complicating intraoperative surgical decision-making. Here, we report a nanopore DNA methylation analysis (NDMA) sequencing approach combined with machine learning for classification of tumor entities that could be used intraoperatively. Methods We analyzed 50 biopsies obtained from biobanked tissue (43, prospective) or sampled at surgery (7, intraoperative) from 20 female and 30 male patients with a median age of 8 y…