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Facteurs impliqués dans le remodelage de la chromatine au cours de la spermiogenèse

Factors involved in chromatin remodelling during spermatogenesis

Resume

Les spermatides rondes sont les cellules issues de la méiose dont le noyau haploïde présente initialement une structure similaire à celle d’une cellule somatique. Au cours de la maturation post-méiotique de la spermatide, ou spermiogenèse, la chromatine subit un remodelage au cours duquel le noyau de la spermatide s’allonge puis se condense pour former le noyau spermatique, dont la chromatine présente une structure très spécifique et très compacte. Lors de ce remodelage, les histones sont remplacées par les protéines de transition puis par les protamines, protéines nucléaires spécifiques du spermatozoïde. Immédiatement avant leur remplacement, les protéines histones sont hyperacétylées. Nous avons entrepris de caractériser précisément l’acétylation des histones cœur du nucléosome au cours de la spermatogenèse murine. Nous avons ainsi montré que, chez la souris, les histones cœur H2A, H2B, H3 et H4 sont hyperacétylées dans les spermatides en cours d’élongation. Nous avons ensuite montré qu’une dégradation des histones déacétylases (HDACs) est responsable de cette augmentation brutale du niveau d’acétylation en début d’élongation. Enfin, chez l’homme, nos données suggèrent qu’un processus semblable est mis en jeu lors de la spermatogenèse normale. De plus, une forte déplétion en cellules germinales, telle qu’elle est observée dans les syndromes des cellules de Sertoli isolées (SCO), est associée a une augmentation très importante de l’acétylation du noyau des cellules de Sertoli. L’ensemble de ces données apporte les bases nécessaires à la compréhension des mécanismes et à l’identification de facteurs impliqués dans les différentes étapes du remodelage postméiotique de la chromatine.

Abstract

Round spermatids are post-meiotic cells with a haploid genome contained in a nucleus, with a structure initially similar to that of the somatic cell nucleus. During spermatogenesis, the spermatid nucleus undergoes drastic remodelling during which it first elongates and then condenses into the very specific and tightly packaged structure of the sperm nucleus. During this remodelling dthe histones are replaced by transition proteins, which, in turn, are replaced by protamines, the specific nuclear proteins of the spermatozoa. Immediately prior to their replacement, the histones are hyperacetylated. The first part of our work was to precisely characterise the changes in histone acetylation during murine spermatogenesis. We have shown that the core histones H2A, H2B, H3 and H4 are hyperacetylated in the elongating spermatids. We have also shown that these changes in acetylation are associated with degradation of the enzymes responsible for histone deacetylation, histone deacetylases or HDACs, while histone acetyl transferases are still present in these cells. The histone acetylation pattern was also investigated during human spermatogenesis, revealing that histone hyperacetylation in the nucleus of elongating spermatids, which appears to be conserved during the course of evolution, also occurs during human spermatogenesis. Moreover, our data obtained from the testes of men with severely altered spermatogenesis, including SCO syndromes (Sertoli Cells Only Syndromes), show that a global hyperacetylation of the Sertoli cell nuclei is associated with an absence of meiotic and post-meiotic cells. This suggests that the global histone acetylation variations observed during spermatogenesis are part of a signalling pathway involving germ cell — Sertoli cell communication. Altogether, these data provide a basis for a better understanding of the mechanisms and identification of the factors involved in post-meiotic remodelling of chromatin.

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Correspondence to Sophie Rousseaux.

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Rousseaux, S., Caron, C., Pivot-Pajot, C. et al. Facteurs impliqués dans le remodelage de la chromatine au cours de la spermiogenèse. Androl. 13, 139–147 (2003). https://doi.org/10.1007/BF03034428

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  • DOI: https://doi.org/10.1007/BF03034428

Mots Clés

  • chromatine
  • spermiogenèse
  • spermatide
  • histones
  • acétylation

Key-Words

  • chromatin
  • spermatogenesis
  • spermatid
  • histones
  • acetylation