H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis.
During meiotic prophase in male mammals, the X and Y chromosomes condense to form a macrochromatin body, termed the sex, or XY, body, within which X- and Y-linked genes are transcriptionally repressed. The molecular basis and biological function of both sex body formation and meiotic sex chromosome inactivation (MSCI) are unknown. A phosphorylated form of H2AX, a histone H2A variant implicated in DNA repair, accumulates in the sex body in a manner independent of meiotic recombination-associated double-strand breaks. Here we show that the X and Y chromosomes of histone H2AX-deficient spermatocytes fail to condense to form a sex body, do not initiate MSCI, and exhibit severe defects in meiotic pairing. Moreover, other sex body proteins, including macroH2A1.2 and XMR, do not preferentially localize with the sex chromosomes in the absence of H2AX. Thus, H2AX is required for the chromatin remodeling and associated silencing in male meiosis.
Fernandez-Capetillo
Oscar
O
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mahadevaiah
Shantha K
SK
Celeste
Arkady
A
Romanienko
Peter J
PJ
Camerini-Otero
R Daniel
RD
Bonner
William M
WM
Manova
Katia
K
Burgoyne
Paul
P
Nussenzweig
André
A
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D023902:Chromosome Pairing / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology*; D006657:Histones / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase; D012728:Sex Chromatin / Q000235:genetics / Q000378:metabolism; D012729:Sex Chromosome Aberrations; D012730:Sex Chromosomes / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000002:abnormalities / Q000378:metabolism* / Q000473:pathology
D002843:Chromatin; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009687:Nuclear Proteins; C085792:Slx protein, mouse; C490091:XLRL protein, human; C490092:Xlr nuclear protein, mouse; D012319:RNA Polymerase II; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse