title: Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B.
abstract: The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.
authors.affiliation: U823, Institut National de la Santé et de la Recherche Médicale INSERM, Institut Albert Bonniot, Université Joseph Fourier, Grenoble F-38700 France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Montellier
authors.forename: Fayçal
authors.initials: F
authors.lastname: Boussouar
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Thierry
authors.initials: T
authors.lastname: Buchou
authors.forename: François
authors.initials: F
authors.lastname: Fenaille
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiota
authors.forename: Alexandra
authors.initials: A
authors.lastname: Debernardi
authors.forename: Patrick
authors.initials: P
authors.lastname: Héry
authors.forename: Sandrine
authors.initials: S
authors.lastname: Curtet
authors.forename: Mahya
authors.initials: M
authors.lastname: Jamshidikia
authors.forename: Sophie
authors.initials: S
authors.lastname: Barral
authors.forename: Hélène
authors.initials: H
authors.lastname: Holota
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bergon
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lopez
authors.forename: Philippe
authors.initials: P
authors.lastname: Guardiola
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.forename: Carlo
authors.initials: C
authors.lastname: Petosa
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gérard
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D005306:Fertilization / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D009707:Nucleosomes; D011479:Protamines / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011479:Protamines; C015786:deoxyribonucleoprotamine; C081018:histone H2B type 1-A
keywords: BRDT; H2AZ; histone eviction; male contraception; male infertility; reprogramming; sex chromosome inactivation