Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells

Sophie Barral, Yuichi Morozumi, Hiroki Tanaka, Emilie Montellier, Jérôme Govin, Maud de Dieuleveult, Guillaume Charbonnier, Yohann Couté, Denis Puthier, Thierry Buchou, Fayçal Boussouar, Takashi Urahama, François Fenaille, Sandrine Curtet, Patrick Héry, Nicolas Fernandez-Nunez, Hitoshi Shiota, Matthieu Gérard, Sophie Rousseaux, Hitoshi KurumizakaSaadi Khochbin*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    91 Citations (Scopus)


    Histone replacement by transition proteins (TPs) and protamines (Prms) constitutes an essential step for the successful production of functional male gametes, yet nothing is known on the underlying functional interplay between histones, TPs, and Prms. Here, by studying spermatogenesis in the absence of a spermatid-specific histone variant, H2A.L.2, we discover a fundamental mechanism involved in the transformation of nucleosomes into nucleoprotamines. H2A.L.2 is synthesized at the same time as TPs and enables their loading onto the nucleosomes. TPs do not displace histones but rather drive the recruitment and processing of Prms, which are themselves responsible for histone eviction. Altogether, the incorporation of H2A.L.2 initiates and orchestrates a series of successive transitional states that ultimately shift to the fully compacted genome of the mature spermatozoa. Hence, the current view of histone-to-nucleoprotamine transition should be revisited and include an additional step with H2A.L.2 assembly prior to the action of TPs and Prms.

    Original languageEnglish
    Pages (from-to)89-101.e8
    JournalMolecular Cell
    Issue number1
    Publication statusPublished - 2017 Apr 6


    • Brdt
    • H2A.Z
    • MCM
    • Nap1L4
    • Npm3
    • spermiogenesis
    • SRCAP
    • subnucleosome
    • TH2B
    • Tip60

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology


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