Genome-wide analysis on content and function of residual nucleosomes in sperm : studies in bovine and human

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YangYang_2013_12_12.pdf (3.83 MB)

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2013

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http://dx.doi.org/10.22029/jlupub-13886

Abstract

It is suggested that at fertilization, spermatozoa transfer both genetic and epigenetic information into the oocyte, e.g. the DNA methylation pattern and various histone modifications. However, the relevance of the sperm epigenome for fertilization and embryogenesis is, so far, for the most part unknown. During spermiogenesis, replacement of DNA-binding histones by protamines is followed by a condensation of the nuclear chromatin resulting in a 10-fold-less volume of the original paternal genome. Interestingly, depending on species, 1% to 15% of nucleosomes remain within the sperm. This thesis aims to analyze whether nucleosome retention in sperm from various species displays general regularities. For this purpose, we analyzed two mammalian species, man and bovine. In addition, we intend to understand the biological impact of nucleosome retention in sperm by applying a genome-wide analysis. In contrast to data available from the literature, we observed only 4.8% nucleosomes in man and 14% nucleosomes in bovine. For the first time, we demonstrated that sperm nucleosomes were prominently associated with repetitive DNA elements, with a significant enrichment in heterochromatic centromere repeats and in retrotransposons, within intergenic and intron sequences. In contrast, nucleosome depletion could be observed predominantly in exon sequences, 5 -and 3 -UTRs and gene promoters, and was associated to simple sequence repeats, low complexity repeats and DNA transposons. Furthermore, nucleosome-retaining genes (preferably in gene bodies) were associated with biological functions, such as RNA- and protein-processing, calcium-ion transport, cell-cell adhesion, membrane and cytoskeletal organization. HOX-genes and genes important for morphogenesis and organ development exhibited nucleosome depletion.Our data revealed a comparable distribution pattern of sperm nucleosomes in both analyzed species and support the hypothesis that sperm nucleosomes might play a role for gene expression in the developing embryo.

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