The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.
Genes Dev
; 27(9): 985-90, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23603901
ABSTRACT
Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases. The median survival of this group of patients after diagnosis is â¼1 yr. Here we show that the levels of H3K27 di- and trimethylation (H3K27me2 and H3K27me3) are reduced globally in H3.3K27M patient samples due to the expression of the H3.3K27M mutant allele. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histonas
/
Regulação Neoplásica da Expressão Gênica
/
Glioma
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Mutação
Limite:
Humans
Idioma:
En
Revista:
Genes Dev
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos