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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The Y chromosome has genome-wide influences over chromatin structure and gene regulation

The Y chromosome has genome-wide influences over chromatin structure and gene regulationIn mammals, the Y chromosome is responsible for determining the male sex by initiating the development of male-specific gonad tissues. Hormones, produced and secreted by the sex organs, are vital for initiating and maintaining sexual dimorphisms. However, differences seen between the sexes are not solely derived from hormones. In fact, sexual differentiation begins in early embryonic development – before hormones have even begun to be produced. Some genes on both autosomal and sex chromosomes are differentially expressed between the sexes, prior to gonad differentiation.2,5  In embryonic stem cells, a XX sex compliment is associated with decreased global DNA methylation compared to XY and X0 cells.15  Sex compliments (XX vs XY) also influences the imprinting of autosomal alleles.6

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Endothelial DNA Methylation Goes With the Flow

Endothelial DNA Methylation Goes With the Flow

Atherosclerosis is an inflammatory disease of the arterial walls, and is the major cause of heart attack and stroke. Atherosclerosis is localized to curves and branches in the vasculature where disturbed blood flow (d-flow) is able to alter gene expression and induce endothelial cell (EC) dysfunction. Our lab’s work focuses on the mechanism by which these gene expression changes occur. We utilize in vivo mouse models of d-flow-induced atherosclerosis that we have developed to determine how blood flow affects vascular biology and disease.2,3

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