Dokument

Zusammenfassung:
Die Spermatogenese ist ein sehr konservierter Prozess von der Fliege bis zu Mammalia, bei dem aus diploiden Spermatogonien haploide Spermatiden entstehen. Bei der Spermatogenese von Mammalia endet die Transkription in frühen, runden Spermatiden. Die für die Spermiogenese benötigten Transkripte werden translational reprimiert und selektiv bei Bedarf translatiert. In Drosophila melanogaster hingegen findet die Transkription translational reprimierter mRNAs bereits in den frühen Spermatozyten statt. Bezüglich des Drosophila-Testes gilt die Hypothese, dass u. a. ein testisspezifischer Transkriptionsfaktor TFIID existiert, der die Transkription der post-meiotisch relevanten Gene mit Hilfe von TATA-Box bindende Protein assoziierten Faktoren (tTAFs) initiiert. Weiterhin wird postuliert, dass der Polycomb-Repressive-Komplex 1 (PRC1) die Expression der Spermiogenese-relevanten Gene bis hin zu den frühen Spermatozyten reprimiert. Mit Unterstützung der tTAFs soll der PRC1 vom Promotor dieser Gene entfernt und zum Nukleolus der Spermatozyten rekrutiert werden, wobei die tTAFs zusätzlich auch an der Transkriptionsaktivierung dieser Gene beteiligt sein sollen. Zusätzlich konnten testisspezifisch exprimierte Bromodomänen-Proteine (tBRD-1, tBRD-2, tBRD-3) identifiziert werden, die in Drosophila-Testes mit Untereinheiten des PRC1 und den tTAFs in Spermatozyten zu kolokalisieren vermögen. Basierend auf diesen Daten ist die Vermutung aufgestellt worden, dass tBRDs an der Transkriptionsaktivierung in Spermatozyten beteiligt sind. Ob die Reprimierenden Komplexe PRC1 und PRC2 auch in Säuger-Testes vorkommen, ist nicht bekannt. In Mammalia ist BRDT das einzig bekannte BRD-Protein, dem eine Rolle bei der Transkriptionsinitiation als auch bei der Reorganisation des Chromatins im Verlauf der Spermatogenese nachgesagt wird. Im ersten Teil dieser Arbeit wurden klassische BRD-Proteine in Testes von Mammalia evaluiert. Die Resultate verweisen darauf, dass die Transkripte für die BRD-Proteine BRD2, BRD8 und TIF1α in frühen runden Spermatiden signifikant angereichert sind. Zudem überlappt die Expression diese Proteine mit dem Auftreten aktiver RNA-Polymerase II. Die Expression der beiden BRD-Proteine BRD3 und SMARCA2 überlappt mit der des Transitionsproteins 1 sowie mit hyperacetyliertem Histon H4. Die experimentellen Studien legen nahe, dass die genannten BRD-Proteine neben BRDT möglicherweise an der Transkription meiotischer und post-meiotischer Gene (BRD2, BRD8, TIF1α) sowie an der Reorganisation des Chromatins innerhalb des Histon-Protamin-Austausches (BRD3, SMARCA2) beteiligt sind. Im zweiten Teil der Arbeit wurde untersucht, ob die klassischen Untereinheiten des PRC1 und PRC2 in Säuger-Testes (Maus und Mensch) existieren. Es konnte gezeigt werden, dass die Transkripte der PRC1-Untereinheiten (Ring1, Bmi1, Scmh1, Cbx2, Cbx8) und des PRC2 (Ezh2, Eed, Suz12) in murinen Testes synthetisiert werden. Die Daten der Transkriptverteilung in Spermatogonien, Spermatozyten und runden Spermatiden erlaubten zudem den Rückschluss, dass der murine PRC1 u. a. aus den Untereinheiten RING1, BMI1 und SCMH1 sowie der PRC2 u. a. aus EZH2, EED und SUZ12 aufgebaut sein könnte. Zudem führt die korrelierende Transkriptverteilung einiger PRC- und BRD-Transkripte zu der Annahme, dass die Neusynthese der PRC-Untereinheiten erforderlich sind für die Repression aller Spermatogenesegene im Verlauf der Spermatidendifferenzierung.

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