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Erschienen in: Reproduktionsmedizin 2/2003

01.04.2003 | Reproduktionsbiologie

Epigenetische Kontrolle der Genaktivität

Grundlagen und neue Erkenntnisse zum Klonen

verfasst von: Dr. med. vet. A. Herrler, V. Zakhartchenko, E. Wolf, H. M. Beier

Erschienen in: Reproduktionsmedizin | Ausgabe 2/2003

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Zusammenfassung

Die individuelle Entwicklung beginnt mit einer befruchteten Eizelle, die bereits die gesamte genetische Information für die Ausbildung eines jeden Zelltyps enthält. Das humane Genom beinhaltet nach derzeitiger Schätzung ca. 35.000 Gene, die für die Differenzierung von mehr als 200 histologisch definierten Gewebetypen verantwortlich sind. Differenzierung einer Zelle bedeutet, dass ein Großteil des Genoms abgeschaltet wird. Der Differenzierungsprozess ist an den genauen Ablauf eines genetischen Expressionsprogramms gebunden, welcher jedoch unter epigenetischer Kontrolle steht. Auf diese Weise wird ein molekulares Gedächtnis geformt, welches die Differenzierung einer jeden Zelle definiert. Hierbei wird nicht die Basensequenz der DNS selbst verändert, sondern ihre Zugängigkeit wird über DNS-Methylierung und Veränderungen der Chromatinstruktur beeinflusst. Diese Mechanismen werden bereits bei der Reifung der Keimzellen eingeleitet. Hierbei kommt es zu deutlichen Unterschieden im Umfang der Methylierung bei Spermien und Eizellen. Ein Teil der Methylierungen ist so fest, dass sie auch noch nach der Befruchtung und bei allen Folgezellen Bestand haben; diese werden als Imprints bezeichnet. In der frühen Embryonalentwicklung finden weitere Veränderungen statt, wobei es zu typisch "mütterlichen" und typisch "väterlichen" Genomunterschieden kommt. Entscheidend sind die Methylierung der DNS sowie die Methylierung oder Azetylierung der Kernproteine, besonders der Histone. Ob und wie diese Prozesse umkehrbar sind und ineinandergreifen ist derzeit ein zentrales Anliegen der Forschung, besonders im Zusammenhang mit den Klonierungsversuchen. Der schwierigste Schritt ist die Rückführung einer adulten Körperzelle auf die Entwicklungsstufe einer Zygote als Basis für die Bildung verschiedener Gewebe oder eines Individuums, wie es erstmals bei dem Schaf Dolly erfolgreich durchgeführt wurde. Limitierender Faktor beim Klonen, also der Herstellung einer totipotenten Zelle aus einem somatischen Zellkern, der in eine enukleierte Oozyte transferiert wurde, scheinen epigenetische Vorgänge zu sein. Fehlsteuerungen in den epigenetischen Regulationsmechanismen können schwerwiegende Folgen, wie zum Beispiel Schizophrenie, Immunkrankheiten oder Krebserkrankungen, haben.
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Metadaten
Titel
Epigenetische Kontrolle der Genaktivität
Grundlagen und neue Erkenntnisse zum Klonen
verfasst von
Dr. med. vet. A. Herrler
V. Zakhartchenko
E. Wolf
H. M. Beier
Publikationsdatum
01.04.2003
Verlag
Springer-Verlag
Erschienen in
Reproduktionsmedizin / Ausgabe 2/2003
Print ISSN: 1434-6931
Elektronische ISSN: 1434-808X
DOI
https://doi.org/10.1007/s00444-003-0398-y

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