Histone H3 lysine 9 methylation occurs rapidly at the onset of random X chromosome inactivation.
Curr Biol
; 12(3): 247-51, 2002 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-11839280
ABSTRACT
In female mammals, a single X chromosome is stably and heritably silenced early in embryogenesis. The inactive X is characterized by asynchronous DNA replication and epigenetic chromatin modifications, including DNA methylation, histone H3/H4 hypoacetylation, and incorporation of a variant histone macroH2A. X inactivation is initiated by a cis-acting RNA molecule, the X-inactive specific transcript (Xist), which coats the chromosome. However, the mechanism by which Xist induces chromosome silencing is poorly understood. An important approach towards answering this question has been to determine the temporal order of epigenetic chromatin modifications in an in vitro model system, differentiating XX embryonic stem (ES) cells, and thereby to identify candidate targets for Xist RNA. To date, these studies have demonstrated that, following accumulation of Xist RNA, the transition to late replication of the X chromosome is the earliest detectable event. H4 hypoacetylation, macroH2A1.2 incorporation, and DNA methylation all occur subsequently. Recently, it has been shown that chromatin of the inactive X is also characterized by methylation of histone H3 at lysine 9 (H3-K9). Here we show that H3-K9 methylation is a very early event in the process of X inactivation, which closely parallels the onset of Xist RNA accumulation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomo X
/
Histonas
/
Mecanismo Genético de Compensação de Dose
/
Lisina
/
Metilação
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Reino Unido