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...

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Detalhes bibliográficos
Autores: Fernandez-Capetillo, Oscar, Mahadevaiah, Shantha K, Celeste, Arkady, Romanienko, Peter J, Camerini-Otero, R Daniel, Bonner, William M, Manova, Katia, Burgoyne, Paul, Nussenzweig, André, capetillo
Formato: artículo
Fecha de publicación:2003
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17705
Acesso em linha:http://hdl.handle.net/20.500.12105/17705
Access Level:acceso abierto
Palavra-chave:Animals
Cell Nucleus
Chromatin
Chromosome Pairing
DNA-Binding Proteins
Gene Silencing
Histones
Male
Meiosis
Mice
Mice, Knockout
Nuclear Proteins
Protein Structure, Tertiary
RNA Polymerase II
Rad51 Recombinase
Sex Chromatin
Sex Chromosome Aberrations
Sex Chromosomes
Spermatocytes
Testis
Descrição
Resumo: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.