CDP/Cux stimulates transcription from the DNA polymerase alpha gene promoter.

Truscott M; Raynal L; Premdas PGoulet BLeduy LBerube GNepveu A

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CDP/Cux stimulates transcription from the DNA polymerase alpha gene promoter.

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CDP/Cux (CCAAT-displacement protein/cut homeobox) contains four DNA binding domains, namely, three Cut repeats (CR1, CR2, and CR3) and a Cut homeodomain. CCAAT-displacement activity involves rapid but transient interaction with DNA. More stable DNA binding activity is up-regulated at the G(1)/S transition and was previously shown to involve an N-terminally truncated isoform, CDP/Cux p110, that is generated by proteolytic processing. CDP/Cux has been previously characterized as a transcriptional repressor. However, here we show that expression of reporter plasmids containing promoter sequences from the human DNA polymerase alpha (pol alpha), CAD, and cyclin A genes is stimulated in cotransfections with N-terminally truncated CDP/Cux proteins but not with full-length CDP/Cux. Moreover, expression of the endogenous DNA pol alpha gene was stimulated following the infection of cells with a retrovirus expressing a truncated CDP/Cux protein. Chromatin immunoprecipitation (ChIP) assays revealed that CDP/Cux was associated with the DNA pol alpha gene promoter specifically in the S phase. Using linker scanning analyses, in vitro DNA binding, and ChIP assays, we established a correlation between binding of CDP/Cux to the DNA pol alpha promoter and the stimulation of gene expression. Although we cannot exclude the possibility that stimulation of gene expression by CDP/Cux involved the repression of a repressor, our data support the notion that CDP/Cux participates in transcriptional activation. Notwithstanding its mechanism of action, these results establish CDP/Cux as an important transcriptional regulator in the S phase.

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《Molecular and Cellular Biology》 |2003年第8期|3013-3028|共16页
作者
Truscott M; Raynal L; Premdas PGoulet BLeduy LBerube GNepveu A;
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作者单位

Molecular Oncology Group, McGill University Health Center and Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3A 1A1.;

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正文语种英语
中图分类分子生物学;
关键词
DNA Polymerase I; Homeodomain Proteins; Nuclear Proteins; Repressor Proteins; DNA聚合酶Ⅰ; 同源域蛋白质类; 核蛋白质类; 阻遏蛋白质类;

CDP/Cux stimulates transcription from the DNA polymerase alpha gene promoter.

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