In mammalian males, the first meiotic prophase is characterized by formation of a separate chromatin domain called the sex body1. In this domain, the X and Y chromosomes are partially synapsed and transcriptionally silenced, a process termed meiotic sex-chromosome inactivation (MSCI)2,3. Likewise, unsynapsed autosomal chromatin present during pachytene is also silenced (meiotic silencing of unsynapsed chromatin, MSUC)2,4,5. 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 dimethylation4, 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.
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We thank T. Jenuwein, A. Schulmeister, F. van Leeuwen, C. Heyting, P.B. Moens, P.D. Adams and H.G. Stunnenberg for providing antibody reagents; J.-F. Spetz, A. Kelly and M. Puschendorf for their help in the generation and initial characterization of H3.1-HA and H3.3-V5 transgenic mice; C. Heyting, A. Pastink and E. de Boer for male meiotic preparations of Sycp1−/− knockout mice; and W.M. Baarends, C. Logie and P.J. Wang for critical reading of the manuscript. Research in the laboratory of A.H.F.M.P. is supported by the Novartis Research Foundation and the NoE network “The Epigenome” (LSHG-CT-2004-503433).
Temporary reduction of nucleosome density in the XY body.
Generation and characterization of H3.3-V5 and H3.1-HA transgenic lines.
Patterns of H3K4, H3K9, H3K27 and H4K20 methylation during prophase I.
Schematic overview of timing of events.
Presence of HirA in XY chromatin during prophase I.
Duration of H3.1/H3.2 loss and positioning in prophase I.
Frequencies of H3.3-V5 incorporation into sex chromosomes during subsequent stages of meiotic prophase and in round spermatids.
Histone H3.1/H3.2 in T70H/T1Wa and Sycp−/− spermatocytes.
About this article
Science China Life Sciences (2016)