title: Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells.
abstract: 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.
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Barral
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France; Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Morozumi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Montellier
authors.affiliation: Université Grenoble Alpes, Inserm U1038, CEA, BIG-BGE, Grenoble 38000, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Govin
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
authors.forename: Maud
authors.initials: M
authors.lastname: de Dieuleveult
authors.affiliation: TGML, platform IbiSA, Aix Marseille Univ, Inserm U1090, TAGC, Marseille 13288, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charbonnier
authors.affiliation: Université Grenoble Alpes, Inserm U1038, CEA, BIG-BGE, Grenoble 38000, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Couté
authors.affiliation: TGML, platform IbiSA, Aix Marseille Univ, Inserm U1090, TAGC, Marseille 13288, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Puthier
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Buchou
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Fayçal
authors.initials: F
authors.lastname: Boussouar
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Urahama
authors.affiliation: Laboratoire d'Etude du Métabolisme des Médicaments, DSV/iBiTec-S/SPI, CEA Saclay, Gif-sur-Yvette 91191 Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Fenaille
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Curtet
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Héry
authors.affiliation: TGML, platform IbiSA, Aix Marseille Univ, Inserm U1090, TAGC, Marseille 13288, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fernandez-Nunez
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiota
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gérard
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.affiliation: CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France. Electronic address: saadi.khochbin@univ-grenoble-alpes.fr.
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D016678:Genome; D006657:Histones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011479:Protamines / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D011479:Protamines; C015786:deoxyribonucleoprotamine; C053886:spermatid transition proteins
keywords: Brdt; H2A.Z; MCM; Nap1L4; Npm3; SRCAP; TH2B; Tip60; spermiogenesis; subnucleosome