Nejire/dCBP-mediated control of H3 acetylation and transcriptional regulation by testis-specific Plus3 domain proteins during Drosophila spermatogenesis
Spermatogenesis describes the development from germ line stem cells to highly specialized sperm. Drosophila melanogaster spermatogenesis is a good model system for chromatin remodelling processes as many of these processes are similar in mammals and in flies. Histone modifications are a prerequisite...
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|Summary:||Spermatogenesis describes the development from germ line stem cells to highly specialized sperm. Drosophila melanogaster spermatogenesis is a good model system for chromatin remodelling processes as many of these processes are similar in mammals and in flies. Histone modifications are a prerequisite for the exchange of histones by protamines during these chromatin remodelling processes but also transcription processes in earlier germ cell stages can be compared. In this thesis, the histone acetyltransferase Nejire/dCBP has been characterised as being responsible for the modification of histone H3 at lysine 18 and lysine 27 during post-meiotic germ cell development as well as in the spermatocyte stage. An RNAi-mediated knock-down revealed that the function of Nejire/dCBP is essential for fertility of male flies. Efficient mRNA synthesis of postmeiotic chromatin components depends on Nejire/dCBP whereas incorporation of protamines into the chromatin does not seem to depend on Nejire/dCBP function. Drosophila spermatogenesis is featured by a special regulation of transcription and translation. While most transcripts are synthesised in spermatocytes, a large portion has to be translationally repressed until required in later stages of germ cell development. Transcriptional regulation is supported by testis-specific variants of the general transcription machinery. This includes among others the tTAFs, the tMAC complex and bromodomain proteins. Bromodomain proteins are able to recognise and bind acetylated lysine residues on N-terminal histone chains. The bromodomain proteins tBRD-1 and tBRD-2 are expressed in spermatocytes and can interact with tTAFs, this might facilitate recruitment of the TFIID complex to certain chromatin areas. Further testis-specific variants of ubiquitously expressed proteins are the Plus3 domain proteins. Here, the expression and function of the testis-enriched proteins tPlus3a and tPlus3b have been examined. Both proteins share the conserved Plus3 domain of Rtf1. RNAseq analysis using RNA from mutant testes revealed that tPlus3a and tPlus3b likely contribute to the regulation of transcription in spermatocytes. Furthermore, genes which also depend on tBRD-1 function were identified. We hypothesise that tPlus3a and tPlus3b regulate a group of genes overlapping with tBRD-1-depending genes but not with genes depending on tTAFs. tPlus3a and tPlus3b might therefore contribute to diversification of transcriptional regulation in spermatocytes.|
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