Search results for "Epigenesis"

Beckwith–Wiedemann syndrome: multiple molecular mechanisms

2006

Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth condition with an increased risk of developing embryonic tumours, such as Wilms' tumour. The cardinal features are abdominal wall defects, macroglossia and gigantism. BWS is generally sporadic; only 10–15% of cases are familial. A variety of molecular aberrations have been associated with BWS. The only mutations within a gene are loss-of-function mutations in the CDKN1C gene, which codes for an imprinted cell-cycle regulator. CDKN1C mutations appear to be particularly associated with umbilical abnormalities, but not with increased predisposition to Wilms' tumour. In the remaining BWS subgroups, a disturbance of the tight epigeneti…

Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

2007

AbstractIntegrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them w…

Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes

2020

Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associ…

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…

Stochastic Loss of Silencing of the Imprinted Ndn/NDN Allele, in a Mouse Model and Humans with Prader-Willi Syndrome, Has Functional Consequences

2013

Genomic imprinting is a process that causes genes to be expressed from one allele only according to parental origin, the other allele being silent. Diseases can arise when the normally active alleles are not expressed. In this context, low level of expression of the normally silent alleles has been considered as genetic noise although such expression has never been further studied. Prader-Willi Syndrome (PWS) is a neurodevelopmental disease involving imprinted genes, including NDN, which are only expressed from the paternally inherited allele, with the maternally inherited allele silent. We present the first in-depth study of the low expression of a normally silent imprinted allele, in path…

Epigenomics in acute cerebrovascular diseases.

2020

Human FOXP3 and cancer.

2010

FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…

The effect of experimental lead pollution on DNA methylation in a wild bird population

2021

Anthropogenic pollution is known to negatively influence an organism’s physiology, behaviour, and fitness. Epigenetic regulation, such as DNA methylation, has been hypothesized as a potential mechanism to mediate such effects, yet studies in wild species are lacking. We first investigated the effects of early-life exposure to the heavy metal lead (Pb) on DNA methylation levels in a wild population of great tits (Parus major), by experimentally exposing nestlings to Pb at environmentally relevant levels. Secondly, we compared nestling DNA methylation from a population exposed to long-term heavy metal pollution (close to a copper smelter), where birds suffer from pollution-related decrease in…

Histone deacetylase inhibitors: apoptotic effects and clinical implications (Review).

2008

It has been shown that epigenetic modifications play an important role in tumorigenesis. Thus, affecting epigenetic tumorigenic alterations can represent a promising strategy for anticancer targeted therapy. Among the key chromatin modifying enzymes which influence gene expression, histone acetyltransferases (HATs) and histone deacetylases (HDACs) have recently attracted interest because of their impact on tumor development and progression. Increased expression of HDACs and disrupted activities of HATs have been found in several tumor types, with a consequent hypoacetylated state of chromatin that can be strictly correlated with low expression of either tumor suppressor or pro-apoptotic gen…

FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies

2010

Abstract Background Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage. Methods Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls. We analyzed in particular the association with the poverty of speech and the intensity of auditory hallucinations. Potential expansion of thre…