Review of nucleosome input into epigenetic inheritance
Changes in environmental conditions such as nutrition, exposure to environmental pollutants or parental care during early postnatal life can affect the development, physiology and fitness of offspring. The mechanisms underlying the transmission of such traits over one or multiple generations are largely unknown but DNA methylation, RNA and nucleosomes have been proposed as mediators of such epigenetic inheritance. At the end of male germ cell development, chromatin is extensively remodelled, resulting in a highly compact nuclear architecture in spermatozoa that is compatible with fertilisation. During this process, nucleosomes are largely removed from the sperm of mammals and humans and replaced by protamines. The EU-funded NUCLEOSOME RETENTION (Dissecting the mechanism of nucleosome retention in mouse spermatozoa) project has reinvestigated this work and other research that challenges the location of the nucleosomes that are retained. Previous research by several groups including the host institution of the NUCLEOSOME RETENTION project has shown that a fraction of nucleosomes retained in mice and humans are usually located at gene regulatory regions of the genome. Another group reported the location of nucleosomes in repetitive regions of the genome of human and bovine spermatozoa. To reassess the sites of nucleosome occupancy in mammalian spermatozoa, project researchers reanalysed the raw data of nucleosome-associated DNA from human and bovine sperm. They found that the published results on bovine and human sperm are confounded by the use of inappropriate computations for analysis. The work has been published in the peer-reviewed journal Developmental Cell in the article ‘Alternative Computational Analysis Shows No Evidence for Nucleosome Enrichment at Repetitive Sequences in Mammalian Spermatozoa’. NUCLEOSOME RETENTION project research results have in part clarified the debate over the position of nucleosomes during mammalian sperm development. Methodologies used and developed have provided a firm knowledge base in computational biology analysis to be applied in future nucleosome mapping in mouse sperm. Importantly, the work has laid the foundations for further functional studies in paternal epigenetic inheritance.
Keywords
Nucleosome, epigenetic inheritance, NUCLEOSOME RETENTION, mammalian sperm, computational biology
