An epigenetic platform to study global DNA methylome and transcriptome in parallel from limited tissue such as early embryo

An epigenetic platform to study global DNA methylome and transcriptome in parallel from limited tissue such as early embryoRecent technological advances and the exponential growth of the field of epigenetics, in particular genome-wide studies, are advancing our knowledge and providing more evidence for the interdependence of epigenetic and genetic variations. The importance of genome-wide epigenetic reprogramming in mammalian germ cells and early embryos has shed light on the pivotal role of epigenetics in modulating genome functions at these critical stages of development. Early embryo development is now considered to be a window of susceptibility to epigenetic reprogramming errors or dysregulation. Therefore, genome-wide profiling of early embryo epigenetics could explain the influence of factors such as the nutritional/metabolic status of the mother or the artificial environment of assisted reproductive technologies (ART). However, the peculiar nature of early embryos, in addition to their scarcity (extremely limited quantities of biological sample), poses formidable technical challenges to study the epigenetic profile of early embryo at a genome-wide scale 1.

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Can epigenetics decode a cell’s history? Linking somatic DNA methylation, DNA repair, and gene expression

Can epigenetics decode a cell's history?  Linking somatic DNA methylation, DNA repair, and gene expressionMammalian Genomic DNA (mainly cytosines, in the doublet CpG) can be covalently modified by methylation, which is layered on the primary genetic information and alters gene expression. There are two patterns of DNA methylation. The first is stable methylation, called imprinting. Imprinting is inherited in a sex-specific fashion and is invariant among individuals and cell types (X inactivation, for example). The second pattern, metastable methylation, is unstable and variable among individuals and cell types and is associated with cancer and aging.1 Both types of these methylation patterns are essential for the cellular storage of large DNA molecules, such as mammalian genomes. In fact, DNA strands 2 meters in length can be compacted into a single 10 microns nucleus of a eukaryotic cell – that’s 3 billion bases in each human cell! Additionally, the compaction of large segments of methylated DNA provides a structural platform that allows selective activation of genes during development and somatic life. Loss of the enzymes responsible for DNA methylation is detrimental to embryo development and generates genome instability.2

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Gene Transcription: Not Always Dictated by Histone Modifications!

Gene Transcription: Not Always Dictated by Histone Modifications!The proper regulation of gene expression is of fundamental importance in the maintenance of normal growth and development.  Misregulation of genes can lead to such outcomes as cancer, diabetes and neurodegenerative disease.  A key step in gene regulation occurs during the transcription of the chromosomal DNA into messenger RNA by the enzyme, RNA polymerase II.

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How Environment Shapes Our Epigenome

How Environment Shapes Our EpigenomeGlobal mapping of the human epigenome has revealed that normal somatic cells exhibit their own unique DNA methylation patterns1. This tissue-specific methylome is established during development and faithfully maintained through subsequent cell divisions, in a process mediated by the enzymes DNMT1 and DNMT3A6. In recent years, there has been a growing interest in the influence of environmental factors in the establishment and maintenance of DNA methylation4.  Many studies have implicated environmental exposure in promoting DNA methylation changes – thereby contributing to alterations in cellular phenotype and disease susceptibility2,8. The reliance of these studies on large epidemiological approaches and in vitro models, however, limits our ability to determine the direct causal relationship between the environment and the human epigenome.

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Seasons influence the methylation profiles of newborns: more evidence that mom’s diet during pregnancy has lasting effects in her offspring.

Seasons influence the methylation profiles of newborns: more evidence that mom's diet during pregnancy has lasting effects in her offspring.Metastable epialleles (ME) are gene alleles that are differentially expressed through epigenetic regulatory mechanisms. The DNA methylation status of an ME is established during embryonic development, and can be maintained later into life. The differential methylation of these MEs contribute to phenotypic diversity between individuals and provides an explanation for the epigenetic variability observed in monozygotic twins. In laboratory animals, studies have shown that maternal dietary intake strongly influences ME epigenetic status. Increased dietary exposure to a methyl-donor prior to, and during pregnancy, leads to hypermethylation at MEs and permanent phenotypic variance. In humans however, it has been challenging to elucidate the potential influence of maternal methyl-donor intake on ME methylation level due to methodological difficulties in precise dietary control in pre-gestational women.

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