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An epigenomic approach to understanding the mechanism of nucleosome retention in mouse spermatozoa

Erkek, Serap. An epigenomic approach to understanding the mechanism of nucleosome retention in mouse spermatozoa. 2013, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_10362

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Abstract

In mammals fusion of sperm and oocyte gives rise to a totipotent embryo. Origin of totipotency of the early embryo is highly debated: whether it is achieved by inheritance of the epigenetic states of the gametes or by reprogramming of such parental epigenetic marks in the embryo.
Oocyte and sperm differ in their potential to transmit epigenetic information. The oocyte is full of maternal transcripts, proteins and its DNA is packed into nucleosomes while a spermatozoon is in highly compact structure and the majority of its histones are exchanged by protamines. It has been determined that in mature sperm histone-to-protamine exchange is not complete, still around 10% and 1% of histones are retained in human and mouse sperm, respectively. During the initial period of my PhD, we and others showed that in human sperm retained histones are not randomly distributed in the genome but to some extent are enriched at loci important for developmental and signaling pathways. We obtained similar findings in mouse sperm at single loci. Nevertheless, genome-wide localization of nucleosomes in mouse sperm and the main principles defining specific nucleosome retention were not known. In my project, the major aim was to determine the logic of nucleosome retention by using mouse sperm as the model system. In addition, I investigated transcript dynamics during late spermatogenesis to identify characteristics of the transcriptomes in maturing germ cells and spermatozoa.
By taking a genome-wide approach we have identified that combinatorial effects of sequence composition, histone variants, histone modifications and gene expression uniquely package sperm DNA. Importantly, H3.3 constitutes the main histone H3 variant retained in mature sperm and localizes to CpG islands. The majority of the genomic regions containing H3.3 are marked by H3K4me3. H3.3 retention in sperm reflects high nucleosome turnover in round spermatids. Canonical histone H3 variants H3.1 and H3.2 are present in low amounts in mature sperm and their retention pattern mostly shows the history from non-replicating round spermatids. GC-rich genomic regions marked by H3K27me3 retain H3.1/H3.2, likely related to low nucleosome turnover in round spermatids. Investigating transcript dynamics during later stages of spermatogenesis showed that overall transcript levels towards sperm development are static. Nevertheless, our data relating changes in gene expression to changes in chromatin states highly suggest for ongoing transcriptional activity during differentiation of spermatids into sperm.
Overall, we identified that histone modification states of retained nucleosomes and spermatozoal RNA pool highly relate to early embryonic gene expression, which argues that sperm carries critical information to the early embryo.
Advisors:Peters, Antoine
Committee Members:Längst, Gernot
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
Item Type:Thesis
Thesis no:10362
Bibsysno:Link to catalogue
Number of Pages:160 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:52
Deposited On:06 May 2013 14:40

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