RNA-Guided Genomic Localization of H2A.L.2 Histone Variant

Naghmeh Hoghoughi (1) , Sophie Barral (1) , Sandrine Curtet (1) , Florent Chuffart (1) , Guillaume Charbonnier (2) , Denis Puthier (2) , Thierry Buchou (1) , Sophie Rousseaux (1) , Saadi Khochbin (1)

1 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 TGML - Transcriptomics and Genomics of Marseille-Luminy

The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.

Mots clés: histone dynamics; testis-specific histone variants; epigenetic inheritance; repetitive elements; centromere

Domaines: Sciences du Vivant [q-bio]; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Naghmeh Hoghoughi, Sophie Barral, Sandrine Curtet, Florent Chuffart, Guillaume Charbonnier, et al.. RNA-Guided Genomic Localization of H2A.L.2 Histone Variant. Cells, 2020, 9 (2), pp.474. ⟨10.3390/cells9020474⟩. ⟨hal-02773006⟩