期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 6, 页码 1859-1864出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409875102
关键词
methylation; prostate cancer; Ezh2; histone H1
资金
- NCI NIH HHS [U01 CA084294, CA84294, CA45290] Funding Source: Medline
- NIGMS NIH HHS [GM3712O] Funding Source: Medline
Changes in the substrate specificities of factors that irreversibly modify the histone components of chromatin are expected to have a profound effect on gene expression through epigenetics. Ezh2 is a histone-lysine methyltransferase with activity dependent on its association with other components of the Polycomb Repressive Complexes 2 and 3 (PRC2/3). Ezh2 levels are increasingly elevated during prostate cancer progression. Other PRC2/3 components also are elevated in cancer cells. Overexpression of Ezh2 in tissue culture promotes formation of a previously undescribed PRC complex, PRC4, that contains the NAD(+)-dependent histone deacetylase SirT1 and isoform 2 of the PRC component Eed. Eed2 is expressed in cancer and undifferentiated embryonic stem (ES) cells but is undetectable in normal and differentiated ES cells. The distinct PRC-s exhibit differential histone substrate specificities. These findings suggest that formation of a transformation-specific PRC complex may have a major role in resetting patterns of gene expression by regulating chromatin structure.
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