title: Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation.
abstract: In mammalian males, the first meiotic prophase is characterized by formation of a separate chromatin domain called the sex body. In this domain, the X and Y chromosomes are partially synapsed and transcriptionally silenced, a process termed meiotic sex-chromosome inactivation (MSCI). Likewise, unsynapsed autosomal chromatin present during pachytene is also silenced (meiotic silencing of unsynapsed chromatin, MSUC). Although it is known that MSCI and MSUC are both dependent on histone H2A.X phosphorylation mediated by the kinase ATR, and cause repressive H3 Lys9 dimethylation, the mechanisms underlying silencing are largely unidentified. Here, we demonstrate an extensive replacement of nucleosomes within unsynapsed chromatin, depending on and initiated shortly after induction of MSCI and MSUC. Nucleosomal eviction results in the exclusive incorporation of the H3.3 variant, which to date has primarily been associated with transcriptional activity. Nucleosomal exchange causes loss and subsequent selective reacquisition of specific histone modifications. This process therefore provides a means for epigenetic reprogramming of sex chromatin presumably required for gene silencing in the male mammalian germ line.
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Godfried W
authors.initials: GW
authors.lastname: van der Heijden
authors.forename: Alwin A H A
authors.initials: AA
authors.lastname: Derijck
authors.forename: Eszter
authors.initials: E
authors.lastname: Pósfai
authors.forename: Maud
authors.initials: M
authors.lastname: Giele
authors.forename: Pawel
authors.initials: P
authors.lastname: Pelczar
authors.forename: Liliana
authors.initials: L
authors.lastname: Ramos
authors.forename: Derick G
authors.initials: DG
authors.lastname: Wansink
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Antoine H F M
authors.initials: AH
authors.lastname: Peters
authors.forename: Peter
authors.initials: P
authors.lastname: de Boer
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D009707:Nucleosomes; D049471:Pachytene Stage; D017434:Protein Structure, Tertiary; D012730:Sex Chromosomes; D013090:Spermatocytes / Q000648:ultrastructure; D014998:Y Chromosome
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes