Ith the double bromodomain-containing protein Brdt that binds acetylated histone H4 resulting in a more relaxed chromatin structure facilitating histone exchange/removal [19, 20].Champroux et al. Basic and Clinical Andrology (2016) 26:Page 3 ofDuring sperm chromatin reorganization, histone exchange, which only supports a supercoiled DNA structure, is accompanied by transient DNA strand breaks that function to relax DNA and eliminate free DNA supercoils formed along the process [24, 25, 28, 29]. These DNA strand breaks have been attributed to the activity of topoisomerase II beta (TOPO2? that has the ability to remove DNA supercoiling [30]. DNA strand breaks are recognized by poly(ADP-ribose) [PAR] polymerases, PARP1 and PARP2, which coordinate TOPO2 ependent DNA decondensation facilitating histone to protamine exchange [31, 32]. Another level of heterogeneity is signified by the observation that in some cell-types nucleosomes contain histone variants [33]. Each canonical histone corresponds to different histones variants, which are homologous proteins of the same gene family. Sequence identity between a variant and its corresponding canonical histones can vary. For example, H3 shares 96 identity with the H3.3 variant and 46 identity with the centromere-specific protein A (CENP-A), another H3 variant. The different primary amino acid sequences confer to histone variants specific structures and their own physicochemical properties. Consequently, histone variants possess different biological functions when compared with canonical histones. It is interesting to note that most histone variants are testis-specific and only expressed in male germ cells during spermatogenesis. This observation highlights rather well the atypical nature of the sperm chromatin organization.From a somatic-like chromatin Anlotinib site organization to a spermspecific chromatin organizationDuring spermatogenesis, germ cells undergo a long process of differentiation to form spermatozoa, highly differentiated cells that consist of a head containing the nucleus and a flagellum allowing them to move towards the oocyte in the female genital tract. This cytodifferentiation process prepares the paternal DNA to be transmitted as a single copy, packaging it tightly to safely withstand the arduous journey in the male and female genital tracts. The transition from a somatic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25447644 like nucleus to a specific spermatozoa nucleus is a lengthy process that starts during mid-spermatogenesis with the meiosis becoming highly visible afterwards with the great cytological changes accompanying spermiogenesis. Although at the end of the spermiogenesis spermatozoa look completely cyto-differentiated, in reality this does not appear to be the case. In fact sperm structures including the nucleus continue to evolve after spermiation especially during the epididymal transit. The passage from a spermatogonia, a diploid cell, to four haploid spermatids is based on the meiotic process. Like mitosis, meiosis induces the DNA to condense in order to separatehomologous chromosomes and chromatids in identical cells. This remodeling of the chromatin during meiosis is allowed by PTM of histones and by insertion of ubiquitous or testis-specific histones variants. These chromatin modifications take part in multiple steps during meiosis including the condensation of chromatids, the repair of the numerous DNA single strand breaks created for the pairing of homologous chromosomes, the sex (or XY) body formation, the substantia.