Die Differenzierung männlicher Keimzellen ist durch ein dynamisches Auftreten von kanonischen TAFs, TAF-Varianten sowie epigenetischen Modifikationen gekennzeichnet

Während der Spermatogenese differenzieren männliche Keimbahn Stammzellen zu Spermien, die das parentale Genom sicher zur Eizelle transportieren können. Dieser Differenzierungsprozess geht in seiner letzten Phase, der Spermiogenese, mit einer massiven Umstrukturierung der Zellen und einer Kompaktieru...

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Bibliographische Detailangaben
1. Verfasser: Klaus, Elisabeth Sabine
Beteiligte: Rathke, Christina (Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2015
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During spermatogenesis, male germline stem cells develop into sperm, which are able to transport the paternal genome safely to the egg. The last phase of this differentiation process is called spermiogenesis. Here cells undergo massive reorganization and the chromatin is compacted by the Histone-to-Protamine-Transition. Transcription is shut down long before this process is completed and many of the proteins needed for the reorganisation of the cells rely on translationally repressed mRNAs. Two variants of TATA Box-Binding Protein-associated factors (TAFs) have been identified to be essential for spermatogenesis. TAF4B and TAF7L could be part of a spermatogenesisspecific transcription factor II D (TFIID)-complex, which drives transcription in spermatids. For TAF7L, the involvement in transcription of spermiogenesis-relevant genes could already be shown. The function of TAF4B in spermatids has not yet been analyzed. Here we can show that the involvement in transcription of spermiogenesis-relevant genes for TAF4B is unlikely. Analyzing further TAF-variants and canonical TAFs with a potential function in human and murine spermatids, the TAFs TAF2, TAF5 and TAF6 can be identified to be expressed during spermiogenesis. For the transcripts of Taf5l, Taf6l, Taf9, Taf10 and Taf12, an accumulation in murine spermatids also points to a function of these factors in transcription processes in these cells. Euchromatin, at which transcription takes place, is characterized by acetylated histones. Here PCAF was identified as the first acetyltransferase, which is expressed in transcriptionally active spermatids. Therefore PCAF could be mediating the histone-acetylation during spermiogenesis. The acetylation of histone H3 is analyzed in murine germ cells, the acetylation of histone H4 is analyzed in murine and human germ cells. In addition the methylation of histone H3 on lysine 79 in murine spermatogenesis is evaluated. Most of these histone modifications appear to have a dual function in transcription and the Histone-to-Protamine-Transition. We postulate the existence of a TFIID-complex in human and murine spermiogenesis, which is composed of canonical and TAF-variants. For transcription the acetylation of histones can be mediated by PCAF and most histones stay in an acetylated state till the Histone-to-Protamine-Transition.