KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation.
Proc Natl Acad Sci U S A
; 107(21): 9671-6, 2010 May 25.
Article
em En
| MEDLINE
| ID: mdl-20457893
Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here we show that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression. Chromatin immunoprecipitation assays applied to human genome tiling arrays in conjunction with RNA microarray revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. Mechanistic analyses showed that KDM8 functioned as a transcriptional activator by inhibiting HDAC recruitment via demethylation of H3K36me2, an epigenetic repressive mark. Tumor array experiments revealed KDM8 is overexpressed in several types of cancer. In addition, loss-of-function studies in MCF7 cells leads to cell cycle arrest. These studies identified KDM8 as an important cell cycle regulator.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fases de Leitura Aberta
/
Proliferação de Células
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Histona Desmetilases
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Ciclina A1
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article