Chromatin remodelling initiation during human spermiogenesis

Abstract

SummaryDuring the last phase of spermatogenesis, spermiogenesis, haploid round spermatids metamorphose towards spermatozoa. Extensive cytoplasmic reduction and chromatin remodelling together allow a dramatic decrease of cellular, notably nuclear volume. DNA packing by a nucleosome based chromatin structure is largely replaced by a protamine based one. At the cytoplasmic level among others the acrosome and perinuclear theca (PNT) are formed. In this study we describe the onset of chromatin remodelling to occur concomitantly with acrosome and PNT development. In spread human round spermatid nuclei, we show development of a DAPI-intense doughnut-like structure co-localizing with the acrosomal sac and sub acrosomal PNT. At this structure we observe the first gradual decrease of nucleosomes and several histones. Histone post-translational modifications linked to chromatin remodelling such as H4K8ac and H4K16ac also delineate the doughnut, that is furthermore marked by H3K9me2. During the capping phase of acrosome development, the size of the doughnut-like chromatin domain increases, and this area often is marked by uniform nucleosome loss and the first appearance of transition protein 2 and protamine 1. In the acrosome phase at nuclear elongation, chromatin remodelling follows the downward movement of the marginal ring of the acrosome. Our results indicate that acrosome development and chromatin remodelling are interacting processes. In the discussion we relate chromatin remodelling to the available data on the nuclear envelope and the linker of nucleoskeleton and cytoskeleton (LINC) complex of spermatids, suggesting a signalling route for triggering chromatin remodelling.

Nuclear envelope remodelling during human spermiogenesis involves somatic B-type lamins and a spermatid-specific B3 lamin isoform

“…Moreover, a gradual decrease of nucleosomes and several histone post-translational modifications start at the apical pole of the nucleus in human round spermatids in a region situated directly under the spreading acrosome (De Vries et al, 2012). Considered together with our results, and those from rodents, showing that the anterior limit of the receding NL appears to be adjacent to the posterior limit of the advancing acrosome, these observations strongly suggest a parallel kinetics between chromatin remodelling and the restructuring of the NL.…”

Characterization of BRD4 during Mammalian Postmeiotic Sperm Development

“…Our mouse IF assay data ( Fig. 7C; see Movie S1D in the supplemental material) and those of a recent study of human spermatids show that acetylated histones in the nucleus are depleted first in the region directly adjacent to the acrosome, where initial DNA compaction occurs (16). Moreover, various chromatin-associated proteins known to be involved in chromatin compaction, such as H1T2, are found in the nucleus adjacent to the acrosome (62).…”

“…7B, right graph). Interestingly, the immunofluorescent signal of hyperacetylated histones was depleted from the nuclear region underlying the acrosome (see Movie S1D in the supplemental material), as was shown in human spermatids (16), and adjacent to the BRD4 ring (Fig. 7C).…”

“…Mouse mutants with aberrant acrosome formation produce abnormal, round-headed sperm that show defective nuclear compaction (11)(12)(13)(14)(15). Moreover, histone removal in human spermatids takes place adjacent to the acroplaxome as the acrosome progressively caps the nucleus (16). These studies suggest that acrosome biogenesis plays a role in sperm head shaping and nuclear compaction, but the mechanisms by which this may happen are unknown.…”

Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go!

“…2016), and inherited paternal chromatin may provide a preferentially accessible structure in the paternal PN that is necessary for rRNA transcription and utilisation by the preimplantation embryo (Steger 1999, De Vries et al . 2012, Rathke et al .…”