DS0405 -

Functional organization of satellite DNAs in the male germline – SPERMATOSAT

Submission summary

Satellite DNAs (satDNAs) are heterochromatic repetitive sequences that represent a large fraction of eukaryotic genomes. Paradoxically however, their functions remain largely unknown for two main reasons. First, for decades, they were considered as "junk" DNA and therefore were not studied and second their characteristics make them difficult to manipulate. However a growing number of studies is now showing that they may have important cellular functions. They are transcriptionally active in a developmental and tissue-specific manner suggesting that they require a tight transcriptional regulation. Moreover, perturbations of human satDNA organization have been linked to diseases such as Facioscapulohumeral Muscular Dystrophy or cancers, underlying the importance of increasing our knowledge about these regions.
The SPERMATOSAT project takes advantage of the Segregation Distorter (SD) system in Drosophila to address the functional relevance of satDNAs. In the SD system, males do not transmit to their progeny a wild-type chromosome that bears a large number of copies (>2000) of a satDNA called Rsp, when the homologous chromosome carries a mutation called Sd. By contrast, this mutation does not affect the transmission of the Rsp satDNA when it contains a few hundred repeats. Thus, in SD males, the strength of the distortion is directly linked to the number of Rsp satDNA repeats. At the cytological level, it has been established that spermatids bearing large Rsp present an abnormally condensed chromatin and are eliminated during the histone-to-protamine transition, a complex chromatin remodeling mechanism that replaces most histones by sperm specific nuclear proteins. Nevertheless, the molecular mechanisms involved in the distortion remain largely unknown.
Using genetics, molecular and cellular tools, the SPERMATOSAT project aims at characterizing the chromatin organization of the Rsp satDNA in the male germ cells and at understanding how it impacts the progression of male germ cell differentiation.
The SPERMATOSAT project will focus on three major aims. The first one will be to characterize in details the cellular events that leads to the elimination, in SD males, of the spermatids that carry a large number of Rsp satDNA copies. The second aim is to determine the modifications of the Rsp satDNA chromatin that could explain the SD phenomenon. Notably, we will use a battery of approaches to study, in control and SD males, the dynamics of Rsp chromatin condensation through spermatogenesis, the chromatin composition and the transcriptional activity of Rsp in male germ cells. The third aim will explore the hypothesis of a checkpoint during the histone-to-protamine transition that eliminates abnormal spermatid nuclei. For that, we will perform a genetic screen to identify modifiers of the cytological SD phenotype. This screen should also help to understand the molecular mechanisms at play in SD males and to identify new genes involved in the histone-to-protamine transition itself.
The SPERMATOSAT project should thus provide new insights into satDNA functions but also help to better understand the constraints of the histone-to-protamine transition on the epigenome of the spermatids.

Project coordination

Raphaëlle DUBRUILLE (Laboratoire de Biométrie et Biologie Evolutive)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LBBE-CNRS Laboratoire de Biométrie et Biologie Evolutive

Help of the ANR 239,749 euros
Beginning and duration of the scientific project: - 42 Months

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