Erasure of the paternal transcription program during spermiogenesis: The first step in the reprogramming of sperm chromatin for zygotic development

Abstract

Male germ cells possess a unique epigenetic program and express a male-specific transcription profile. However, when its chromatin is passed onto the zygote, it expresses an transcription/epigenetic program characteristic of the zygote. The mechanism underlying this reprogramming process is not understood at present. In this study, we show that an extensive range of chromatin factors (CFs), including essential transcription factors and regulators, remodeling factors, histone deacetylases, heterochromatin-binding proteins, and topoisomerases, were removed from chromatin during spermiogenesis. This process will erase the paternal epigenetic program to generate a relatively naive chromatin, which is likely to be essential for installation of the zygotic developmental program after fertilization. We have also showed that transcription termination in male germ cells was temporally correlated with CF dissociation. A genome-wide CF dissociation will inevitably disassemble the transcription apparatus and regulatory mechanism and lead to transcription silence. Based on data presented in this and previous studies (Sun et al., Cell Research [2007] 17:117-134), we propose that paternal-zygotic transcription reprogramming begins with a genome-wide CF dissociation to erase the existing transcription program in later stages of spermatogenesis. This will be followed by assembling of the zygotic equivalent after fertilization. The transcription/epigenetic program of the male germ cell is transformed into a zygotic one using an erase-and-rebuild strategy similar to that used in the maternal-zygotic transition. It is also noted that transcription is terminated long after meiosis is completed and before chromatin becomes highly condensed during spermatogenesis. The temporal order of these events suggests that transcription silence does not have to be coupled to meiosis or chromatin condensation.

Histone H3.3 regulates dynamic chromatin states during spermatogenesis

“…During spermatogenesis, a complex interplay of histone posttranslational modifications (PTMs) take place in the nuclei of immature germ cells as they develop into mature spermatozoon (Chen et al, 1998;Godmann et al, 2007;Lewis et al, 2003;Payne and Braun, 2006;Rathke et al, 2013;Tachibana et al, 2007;van der Heijden et al, 2006;Zheng et al, 2008). Together with such histone PTMs, histone variants play a major role in the protamine transition and chromatin reorganization process during spermatogenesis, and many histone variants of histone H1 (H1t, H1T2 HILS1), H2A and H2B (TH2A, TH2B, ssH2B, H2A.B.bd, H2BL1, H2BL2, H2AL1-H2AL3) and H3 (H3t, H3.3) become expressed in specific germ cell types or are testes-specific (Lewis et al, 2003;Rathke et al, 2013).…”

Decrease in spermatic parameters of mice treated with hydroalcoholic extract Tropaeolum tuberosum “mashua”

“…In spermatogenesis, transcription is strongly activated during step 7 round spermatids, decreases sharply in 8, 9 step and at 10 step is undetectable (Zheng et al 2008). In sperm nuclear murine mRNA species, proteins are initially detected in step 7 round spermatids (Mali et al 1989), a stage corresponding to the T. tuberosum 21-days exposed group.…”

“…Mi et al (2007) observed in vitro that phenethyl isothiocyanate (PEITC) binds covalently to cellular proteins and induces apoptosis in cancer cell lines. Isothiocynates present in T. tuberosum could be acting on transcription regulatory, remodeling factors, histone deacetylases, heterochromatin binding proteins and/or topoisomerase in order to prevent gene transcription (Zheng et al 2008). Johns et al (1982) suggested that T. tuberosum has an estrogenic effect, however, sperm transport within and through epididymis is facilitated by the movements of efferent ducts epithelial cells cilia (Ilio & Hess 1994).…”

Histone variant H3.3–mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos

“…This developmental process requires the zygotic genome activation (ZGA) to allow for the transition from specified germ cells to a totipotent embryo, in which both paternal and maternal genomes undergo dramatic epigenetic reprogramming regulated by maternal factors [3]. Overcoming chromatin-mediated transcriptional repression of paternal and maternal genomes is thought to be the first major step to initiate zygotic gene expression after fertilization [4][5][6][7][8][9].…”

“…This developmental process requires the zygotic genome activation (ZGA) to allow for the transition from specified germ cells to a totipotent embryo, in which both paternal and maternal genomes undergo dramatic epigenetic reprogramming regulated by maternal factors [3]. Overcoming chromatin-mediated transcriptional repression of paternal and maternal genomes is thought to be the first major step to initiate zygotic gene expression after fertilization [4][5][6][7][8][9].The mammalian sperm genome is packaged into highly condensed chromatin consisting primarily of protamine but 5-15% residual histones. Following fertilization, ZGA occurs first in the paternal genome (male pronucleus) at the 1-cell stage embryo, while activation of the maternal genome is usually delayed and occurs at the 2-cell stage in mice [10][11][12][13].…”