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Dynamisches Epigenom als Vermittler zwischen Umwelt und Genom

Dynamic epigenome as interface between environment and genome

Zusammenfassung

Die Bedeutung des epigenetischen Zustands von Zellen (Epigenom) als Vermittler zwischen dynamischer Umwelt und vererbtem statischem Genom wird immer deutlicher. Wesentliche Mediatoren dabei sind das Chromatin und kovalente DNA-Modifikationen (Methylierungen). Die Veränderung des Epigenoms während der Ontogenese bildet die Grundlage der zelltypspezifischen Genexpression eines Organismus und ist Ausdruck eines hochkomplexen Prozesses. Epigenetische Aberrationen können ähnliche Konsequenzen wie eine Genfunktion beeinflussende genomische Veränderungen haben. Laut jüngsten Daten ist das Epigenom dynamisch und kann auf Umwelteinflüsse reagieren. Dies ist nicht nur auf den Expositionszeitraum beschränkt, sondern kann im weiteren Verlauf des Lebens nachweisbar sein. Im vorliegenden Beitrag werden der Einfluss chemischer Agenzien sowie von Verhaltensweisen auf das Epigenom dargestellt. Es ist absehbar, dass die Exposition gegenüber verschiedenen Umweltfaktoren/Xenobiotika zu interindividuellen phänotypischen Unterschieden sowie unterschiedlichen Suszeptibilitäten gegenüber Krankheiten und Verhaltenspathologien führen kann. Obwohl nach derzeitigem Verständnis die Bedeutung epigenetischer Mechanismen für den Stoffwechsel von Xenobiotika gering ist, wird die Epigenetik bei der Beurteilung des Gefährdungspotenzials von Chemikalien an Bedeutung gewinnen.

Abstract

The epigenome serves as an interface between the dynamic environment and the inherited static genome. It is comprised of chromatin and a covalent modification of DNA by methylation. The epigenome is sculpted during development to shape the diversity of gene expression programs in the organism’s different cell types by a highly organized process. Epigenetic aberrations have consequences similar to those of genetic polymorphisms, resulting in variations in gene function. Recent data suggest that the epigenome is dynamic and is therefore responsive to environmental signals, not only during the critical periods in development but also later in life. It is postulated here that not only chemicals but also exposure to social behavior, such as maternal care, may affect the epigenome. It is proposed that exposure to different environmental agents could lead to interindividual phenotypic diversity as well as to varying susceptibility to disease and behavioral pathologies. Interindividual differences in the epige­netic state could also affect susceptibility to xenobiotics.

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Abbreviations

cAMP:

Zyklisches Adenosinmonophosphat

CBP :

„CREB-binding protein“

CpG:

Cytosinphosphatidylguanosin

CREB:

„cAMP response element binding“

CRF:

„corticotropin releasing factor“

DNMT:

DNA Methyltransferase

GR-Gen:

Glukokortikoidgen

HAT:

Histon-Azetyl-Transferase

HDAC:

Histondeazetylase

HPA:

„hypothalamo-pituitary-adrenal“

5-HT:

5-Hydroxytryptamin, Serotonin

MBD:

Methyliertes DNA bindendes Protein

NGFI-A:

„nerve growth factor-inducible A“

PKA:

Proteinkinase A

SAM:

S-Adenosyl-Methionin

TF:

Transkriptionsfaktor

TSA :

Trichostatin A

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Szyf, M. Dynamisches Epigenom als Vermittler zwischen Umwelt und Genom. medgen 21, 7–13 (2009). https://doi.org/10.1007/s11825-009-0145-z

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Schlüsselwörter

  • Epigenom
  • DNA-Methylierung
  • DNA-Demethylierung
  • Epigenetik
  • Xenobiotika

Keywords

  • Epigenome
  • DNA methylation
  • DNA demethylation
  • Epigenetics
  • Xenobiotics