Histone variants: essential actors in male genome programming

Abstract

Prior to its transmission to the offspring, the male genome has to be tightly compacted. A genome-scale histone eviction and the subsequent repackaging of DNA by protamines (Prms) direct this essential genome condensation step. The requirement for male germ cells to undergo such a dramatic and unique genome reorganization explains why these cells express the largest number of histone variants, including many testis-specific ones. Indeed, an open chromatin, nucleosome instability and a facilitated process of histone disassembly are direct consequences of the presence of these histone variants in the chromatin of male germ cells. These histone-induced changes in chromatin first control a stage-specific gene expression program and then directly mediate the histone-to-Prm transition process. This review aims at summarizing and discussing a series of recent functional studies of male germ cell histone variants with a focus on their impact on the process of histone eviction and male genome compaction.

Histone variants: critical determinants in tumour heterogeneity

“…In addition to canonical histones that are the building blocks of nucleosomes, the human genome encodes a number of histone variants of the H3, H2A and H2B types. Many of these variants are predominantly or exclusively expressed in spermatogenic cells [14]. The reason is that the final stages of male germ cell differentiation involve one of the most dramatic chromatin remodelling events, characterized by an almost genome-wide eviction of histones and their replacement by protamines [29].…”

“…Functional, biochemical and structural analyses of these histone variants showed that many of them present the ability to generate unstable nucleosomes. This is true for H3, H2B and H2A variants [14]. Taking into account the final dismantlement of chromatin in post-meiotic spermatogenic cells, before the generation of mature spermatozoa, one can easily understand why most of these variants confer nucleosome instability.…”

“…Factors capable of sustaining enhanced chromatin dynamics seem to also improve cell reprogramming [11]. Chromatin dynamics could be directly modulated by canonical replicationdependent histones through the control of their assembly during DNA replication, as well as through induced histone degradation and histone under-dosage or independently, through the assembly of a specific class of histone variants [12][13][14][15][16].…”

Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark

“…Subsequent post-meiotic differentiation of gametes, especially in the paternal germline, is associated with a dramatic reorganization of chromatin [ 19 ]. This begins with a wave of hyperacetylation of histones, which are subsequently evicted and replaced sequentially by transition proteins followed by protamines, which are small, highly basic, sperm-specific proteins [ 20 – 25 ]. This unique, male gamete-specific mechanism of chromatin compaction allows for a dramatic change in cell size and morphology that culminates with formation of the mature spermatozoa.…”

Cstf2t Regulates expression of histones and histone‐like proteins in male germ cells

“…To accomplish genome compaction, germ cells exchange the somatic cohort of histone proteins, first with testis-specific histones, second with transition proteins, and finally with protamines (Bao and Bedford, 2016; Barral et al, 2017; Bošković and Torres-Padilla, 2013; Hoghoughi et al, 2017; Pradeepa and Rao, 2007; Sassone-Corsi, 2002; Wang et al, 2017). These changes in chromatin packaging require precise deployment of the testis-specific histones and histone-like proteins such as protamines (collectively, “histone-like genes”) to make sperm cells that are competent for fertilization (Churikov et al, 2004; Govin et al, 2004; Meistrich et al, 2003; Pradeepa and Rao, 2007).…”