TY - JOUR
T1 - Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation
AU - Van Der Heijden, Godfried W.
AU - Derijck, Alwin A.H.A.
AU - Pósfai, Eszter
AU - Giele, Maud
AU - Pelczar, Pawel
AU - Ramos, Liliana
AU - Wansink, Derick G.
AU - Van Der Vlag, Johan
AU - Peters, Antoine H.F.M.
AU - De Boer, Peter
N1 - Funding Information:
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).
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
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U2 - 10.1038/ng1949
DO - 10.1038/ng1949
M3 - Article
C2 - 17237782
AN - SCOPUS:33846590537
SN - 1061-4036
VL - 39
SP - 251
EP - 258
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -