Epigenetics 

About: Epigenetics is an academic journal published by Landes Bioscience. The journal publishes majorly in the area(s): DNA methylation & Epigenetics. It has an ISSN identifier of 1559-2294. Over the lifetime, 1842 publications have been published receiving 82360 citations. The journal is also known as: Epigenetic theory.

Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

Abstract: Background: In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal (HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression. Objective: To study this in humans, relationships between prenatal exposure to maternal mood and the methylation status of a CpG-rich region in the promoter and exon 1F of the human GR gene (NR3C1) in newborns and HPA stress reactivity at age 3 months were examined. Methods: The methylation status of a CpG-rich region of the NR3C1 gene, including exon 1F, in genomic DNA from cord blood mononuclear cells was quantified by bisulfite pyrosequencing in infants of depressed mothers treated with a serotonin reuptake inhibitor antidepressant (SRI) (n=33), infants of depressed non treated mothers (n=13) and infants of non depressed/non treated mothers (n=36). To study the functional implications of the newborn methylation status of NR3C1 in ...

Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray

Abstract: DNA methylation, an important type of epigenetic modification in humans, participates in crucial cellular processes, such as embryonic development, X-inactivation, genomic imprinting and chromosome stability. Several platforms have been developed to study genome-wide DNA methylation. Many investigators in the field have chosen the Illumina Infinium HumanMethylation microarray for its ability to reliably assess DNA methylation following sodium bisulfite conversion. Here, we analyzed methylation profiles of 489 adult males and 357 adult females generated by the Infinium HumanMethylation450 microarray. Among the autosomal CpG sites that displayed significant methylation differences between the two sexes, we observed a significant enrichment of cross-reactive probes co-hybridizing to the sex chromosomes with more than 94% sequence identity. This could lead investigators to mistakenly infer the existence of significant autosomal sex-associated methylation. Using sequence identity cutoffs derived from the sex methylation analysis, we concluded that 6% of the array probes can potentially generate spurious signals because of co-hybridization to alternate genomic sequences highly homologous to the intended targets. Additionally, we discovered probes targeting polymorphic CpGs that overlapped SNPs. The methylation levels detected by these probes are simply the reflection of underlying genetic polymorphisms but could be misinterpreted as true signals. The existence of probes that are cross-reactive or of target polymorphic CpGs in the Illumina HumanMethylation microarrays can confound data obtained from such microarrays. Therefore, investigators should exercise caution when significant biological associations are found using these array platforms. A list of all cross-reactive probes and polymorphic CpGs identified by us are annotated in this paper.

Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome.

Abstract: DNA methylation is the most studied epigenetic mark and CpG methylation is central to many biological processes and human diseases. Since cancer has highlighted the contribution to disease of aberr...

Epigenetics: A Historical Overview

Abstract: In the first half of the twentieth century, developmental biology and genetics were separate disciplines. The word epigenetics was coined by Waddington to link the two fields. Epigenetics could be broadly defined as the sum of all those mechanisms necessary for the unfolding of the genetic programme for development. Several decades later specific mechanisms were proposed in which information was superimposed on DNA sequences. In particular, it was suggested that 5-methyl cytosine had a role in controlling gene expression, and also that the pattern of methylation was heritable. These predictions are now supported by a large body of evidence which shows that methylation is strongly associated with gene silencing in a variety of biological contexts. There are now also many examples of epigenetic inheritance through the germ line There are several other important epigenetic mechanisms involving chromatin and histone modifications, and also the expanding field of regulatory RNAs. The human epigenome project will unravel the pattern of DNA methylation in different tissues, and will this determine whether the regulation of gene expression is at the level of DNA or chromatin, or both.

Histone Deacetylase Inhibitors for Cancer Therapy

Abstract: The epigenome of cancer cells is determined by DNA methylation and an array of post-translational modifications of the core histones. Epigenetic abnormalities are commonly found in human tumors and importantly, they can be reversed by pharmacologic inhibitors. Histone deacetylase inhibitors (HDACIs) represent one of the most promising epigenetic treatments for cancer. HDACIs have emerged as promising targets for cancer therapy because they reactivate the transcription of multiple genes that are silenced in human tumors and they show pleiotropic anti-tumor effects selectively in cancer cells. HDACIs are well-tolerated and several show promising anti-tumor activity. While gene transcription has been considered to be the major target of HDACIs, inhibition of acetylation of non-histone proteins is now emerging as a novel basis for their anti-tumor effects. In this review, we discuss new insights into the molecular mechanism of HDACIs, their current status of clinical development, and possible future uses in cancer therapy.