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Establishment of test systems for the identification of consumer-related substances with epigenetic activity
Project
Project code: BfR-CPS-08-1322-593
Contract period: 01.03.2014
- 31.12.2017
Purpose of research: Basic research
The term epigenetics describes the phenomenon whereby inheritable changes in gene expression cannot be directly related to changes within the DNA nucleotide sequence. Such changes are usually the result of covalent histone modifications or of DNA-methylation. Throughout a lifetime this so called ‘epigenetic code’ is subject to orchestrated and well defined changes. This is especially true for prenatal development. Here genome wide epigenetic changes lead to tissue- and lineage-specific gene expression patterns which are vital for the further development of the embryo. But also in the adult organism epigenetic changes play an essential role in organ homeostasis as well as for the development of pathological conditions, including cancer. Indeed, within the last years it became obvious that many disorders and diseases are related to epigenetic effects. For example several cancers are accompanied by changed patterns of DNA-methylation, which can be used as prognostic markers. More worryingly it appears that epigenetic alterations can be triggered by prenatal exposure to toxicants. The respective adverse effects comprise developmental defects as well as diseases such as a predisposition for certain types of cancer. However, despite its importance the toxicological understanding of adverse epigenetic events is rather rudimentary. Therefore this project started to systematically analyse the impact off different epigenetic active substances on the embryonic stem cell test. The substances tested were all found to induce similar changes of DNA-(hydroxy)methylation and interacted specifically with chromatin-modifying enzymes. Building on these results the project shall further elucidate the mechanisms and effects of epigenetically active substances and identify suitable biomarkers, respectively.
Section overview
Subjects
- Biotechnology
