Distinctions in the specificity of E2F function revealed by gene expression signatures

被引:61
作者
Black, EP
Hallstrom, T
Dressman, HK
West, M
Nevins, JR [1 ]
机构
[1] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA
[2] Duke Univ, Dept Mol Genet & Microbiol, Med Ctr, Durham, NC 27710 USA
[3] Duke Univ, Inst Stat & Decis Sci, Durham, NC 27710 USA
关键词
DNA microarray; transcriptional control;
D O I
10.1073/pnas.0504300102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The E2F family of transcription factors provides essential activities for coordinating the control of cellular proliferation and cell fate. Both E2F1 and E2F3 proteins have been shown to be particularly important for cell proliferation, whereas the E2F1 protein has the capacity to promote apoptosis. To explore the basis for this specificity of function, we used DNA microarray analysis to probe for the distinctions in the two E2F activities. Gene expression profiles that distinguish either E2F1- or E2F3-expressing cells from quiescent cells are enriched in genes encoding cell cycle and DNA replication activities, consistent with many past studies. E2F1 profile is also enriched in genes known to function in apoptosis. We also identified patterns of gene expression that specifically differentiate the activity of E2F1 and E2F3; this profile is enriched in genes known to function in mitosis. The specificity of E2F function has been attributed to protein interactions mediated by the marked box domain, and we now show that chimeric E2F proteins generate expression signatures that reflect the origin of the marked box, thus linking the biochemical mechanism for specificity of function with specificity of gene activation.
引用
收藏
页码:15948 / 15953
页数:6
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