Search results for "Epigenomic"
showing 10 items of 83 documents
Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells
2021
The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily pr…
Type IV Laryngotracheoesophageal Cleft Associated with Type III Esophageal Atresia in 1p36 Deletions Containing the RERE Gene: Is There a Causal Role…
2018
The causes of embryological developmental anomalies leading to laryngotracheoesophageal clefts (LTECs) are not known, but are proposed to be multifactorial, including genetic and environmental factors. Haploinsufficiency of the RERE gene might contribute to different phenotypes seen in individuals with 1p36 deletions. We describe a neonate of an obese mother, diagnosed with type IV LTEC and type III esophageal atresia (EA), in which a 1p36 deletion including the RERE gene was detected. On the second day of life, a right thoracotomy and extrapleural esophagus atresia repair were attempted. One week later, a right cervical approach was performed to separate the cervical esophagus from the tra…
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…
Caracterización clínica y epigenomica de la Hidradenitis Superlativa
2022
La Hidradenitis Supurativa (HS), también conocida como acné́ inverso o enfermedad de Verneuil, es una enfermedad dermatológica crónica, inflamatoria, recurrente y progresiva que afecta a las áreas de vello con mayor presencia de glándulas apocrinas. Esta enfermedad perjudica de forma severa la calidad de vida del paciente, ya que además de ser un proceso patológico de elevada importancia, su repercusión no es únicamente psicológica, sino que también lleva asociada una limitación física, de las relaciones interpersonales, de autoestima y de la percepción de la imagen personal y publica. Actualmente no se sabe con exactitud la genética que provoca esta enfermedad, pero se ha estudiado que, a …
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…