In human and mouse cells, DNA wraps around a protein called histone, folds regularly, and is stored in a small nucleus.This DNA-protein complex is commonly referred to as chromatin.In sperm, more than 90% of this histone is replaced by a small protein called protamine, which causes the DNA to fold even more compactly, resulting in high chromatin aggregation and sperm nuclei that are a fraction of the size of normal cell nuclei. Become.
This histone protamine substitution and chromatin aggregation are essential for sperm fertility, while the location and function of the few remaining histones in the sperm genome has been controversial for many years.To elucidate, it is necessary to uniformly elute chromatin from the nucleus and analyze it, but sperm chromatin is very hard and cannot be uniformly eluted by the conventional method, so it was difficult to evaluate.
This time, the research team of Kosuke Yamaguchi, a graduate student of the University of Tokyo, and Yuki Okada, has developed a method to uniformly solubilize sperm chromatin by treating sperm with nucleoplasmin, which has the property of removing protamine, and sperm histones. It made it possible to evaluate the localization more accurately.In addition, as a result of localization analysis (next-generation sequencing analysis) using this method, sperm histones have undergone specific genomic regions depending on the status of modifications (acetylation, methylation, phosphorylation, ubiquitination, etc.). It was clarified that it is regularly localized in.
The mechanism by which the phenotype and gene expression level are changed without changing the genomic DNA sequence is called the epigenome.In recent years, the "epigenome inheritance" phenomenon, in which the father's living environment and habits are transmitted to children via sperm, has attracted a great deal of attention, and the results of this research are expected to provide useful insights for elucidating the mechanism.
Paper information:[Cell Reports] Re-evaluating the localization of sperm-retained histones revealed the modification-dependent accumulation in specific genome regions
