Sperm histone mediated epigenetic inheritance†

During spermatogenesis, majority of the histones are replaced by protamines to enable the compaction of the sperm chromatin for efficient delivery into the oocyte. Even after the gross histone replacement, some histones are retained in the sperm ranging from 1% to 15% across mammalian species. The post-translational modifications (PTMs), present on the retained histones of the sperm regulate the embryonic development, post fertilization, making them the suitable candidate for paternal epigenetic inheritance. The retained sperm histones are shown to be distributed on the CpG sites of genes related to embryonic development and also on the gene desert regions, however, they vary in their PTM marks. Further, the exact mechanism for histone retention remains elusive. Also, the mechanism for specific localization and crosstalk of sperm retained histone with DNA methylation and non-coding RNA remains elusive. In this review, we discuss the possible mechanisms of histone retention, their differential localization into euchromatic and heterochromatic chromatin domains and the histone-driven epigenetic inheritance in mammalian sperm. The mechanistic insights of histone to protamine transition are also explored. Further, the PTMs on histone and protamines and their roles in histone-mediated epigenetic inheritance is also explored.