Search results for "Epigenomics"
showing 10 items of 78 documents
A familial disorder of altered DNA-methylation
2014
BackgroundIn a subset of imprinting disorders caused by epimutations, multiple imprinted loci are affected. Familial occurrence of multilocus imprinting disorders is rare.Purpose/objectiveWe have investigated the clinical and molecular features of a familial DNA-methylation disorder.MethodsTissues of affected individuals and blood samples of family members were investigated by conventional and molecular karyotyping. Sanger sequencing and RT-PCR of imprinting-associated genes (NLRP2, NLRP7, ZFP57, KHDC3L, DNMT1o), exome sequencing and locus-specific, array-based and genome-wide technologies to determine DNA-methylation were performed.ResultsIn three offspring of a healthy couple, we observed…
Obesity and Cardiometabolic Risk Factors : from Childhood to Adulthood
2021
Obesity has become a major epidemic in the 21st century. It increases the risk of dyslipidemia, hypertension, and type 2 diabetes, which are known cardiometabolic risk factors and components of the metabolic syndrome. Although overt cardiovascular (CV) diseases such as stroke or myocardial infarction are the domain of adulthood, it is evident that the CV continuum begins very early in life. Recognition of risk factors and early stages of CV damage, at a time when these processes are still reversible, and the development of prevention strategies are major pillars in reducing CV morbidity and mortality in the general population. In this review, we will discuss the role of well-known but also …
To Be or Not to Be a Germ Cell: The Extragonadal Germ Cell Tumor Paradigm
2021
In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigene…
Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.
2021
We would like to thank all the families that participated in these studies for their generous contribution. Detailed acknowledgements and funding can be found in Sup plementary Material.
How does the Mediterranean diet promote cardiovascular health? Current progress toward molecular mechanisms
2014
Epidemiological evidence supports a health-promoting effect of the Mediterranean Diet (MedDiet), especially in the prevention of cardiovascular diseases. These cardiovascular benefits have been attributed to a number of components of the MedDiet such as monounsaturated fatty acids, antioxidant vitamins and phytochemicals. However, the underlying mechanisms remain unknown. Likewise, little is known about the genes that define inter-individual variation in response to the MedDiet, although the TCF7L2 gene is emerging as an illustrative candidate for determining relative risk of cardiovascular events in response to the MedDiet. Moreover, omics technologies are providing evidence supporting pot…
Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature
2015
Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and d…
Epigenomic k-mer dictionaries: shedding light on how sequence composition influences in vivo nucleosome positioning
2014
Abstract Motivation: Information-theoretic and compositional analysis of biological sequences, in terms of k-mer dictionaries, has a well established role in genomic and proteomic studies. Much less so in epigenomics, although the role of k-mers in chromatin organization and nucleosome positioning is particularly relevant. Fundamental questions concerning the informational content and compositional structure of nucleosome favouring and disfavoring sequences with respect to their basic building blocks still remain open. Results: We present the first analysis on the role of k-mers in the composition of nucleosome enriched and depleted genomic regions (NER and NDR for short) that is: (i) exhau…
Applications of alignment-free methods in epigenomics
2013
Epigenetic mechanisms play an important role in the regulation of cell type-specific gene activities, yet how epigenetic patterns are established and maintained remains poorly understood. Recent studies have supported a role of DNA sequences in recruitment of epigenetic regulators. Alignment-free methods have been applied to identify distinct sequence features that are associated with epigenetic patterns and to predict epigenomic profiles. Here, we review recent advances in such applications, including the methods to map DNA sequence to feature space, sequence comparison and prediction models. Computational studies using these methods have provided important insights into the epigenetic reg…
Assessment of computational methods for the analysis of single-cell ATAC-seq data
2019
Abstract Background Recent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysis presents unique methodological challenges. scATAC-seq experiments sample DNA, which, due to low copy numbers (diploid in humans), lead to inherent data sparsity (1–10% of peaks detected per cell) compared to transcriptomic (scRNA-seq) data (10–45% of expressed genes detected per cell). Such challenges in data generation emphasize the need for informative features to assess cell heterogeneity at the chromatin level. Results We present a benchmarking framework that …
Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection
2015
ABSTRACT The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and in situ proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized …