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Imprint
2009: Development of a method suited to identify epigenetic effects in cells in culture upon exposure to low doses of model compounds, 2010: Investigation of epigenetic effects of consumer product-related model compounds in vitro
Project
Project code: BfR-PRS-08-1322-420
Contract period: 01.01.2009
- 31.12.2010
Purpose of research: Applied research
2009: Adverse effects of xenobiotics may result, for instance, from inhibition of enzymes, from disruption of signal transduction cascades or from direct modification of coding DNA. Recent studies recovered that chemical compounds could also affect the metabolism by varying gene expression profiles at the level of epigenetic mechanisms. These heritable phenomena that regulate gene expression without altering the DNA code contribute to various tissue differentiation processes, genomic imprinting and inactivation of the X chromosome. Changes in the expression profile of certain genes based on epigenetic mechanisms are due to modulation of histon acetylation/deacetylation or methylation/demethylation of cytosine bases in CpC islands within gene promotor regions. There is mounting experimental evidence that cellular histone modification and DNA methylation changes upon exposure to various xenobiotics. It was also observed that these induced epigenetic alterations often occur upon exposure of cells to low doses of compounds. 2010: Epigenetics specify the regulation of gene expression, independent on the genetic code. It encompasses DNA methylation as well as different posttranslational histone modifications (e.g. acetylation, methylation, phosphorylation etc.). In conjunction with non-coding RNAs these mechanisms allow the establishment of cell type characteristic gene expression pro-files. Especially, regulatory and differentiation processes are highly susceptible to epigenetic alterations (genomic imprinting, X chromosome inactivation). Different xenobiotics have been attributed to induce epigenetic changes in certain cell types. Differences in the resulting gene expression profiles can be explained based on changes in DNA methylation patterns, as well as in altered posttranslational histone modifications. A transcriptional deregu-lation might result in disturbance of endogenous pathways.
Section overview
Subjects
- Biotechnology
