Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Truscott, M. et al.

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

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.[1]

References

CDP/Cux stimulates transcription from the DNA polymerase alpha gene promoter. Truscott, M., Raynal, L., Premdas, P., Goulet, B., Leduy, L., Bérubé, G., Nepveu, A. Mol. Cell. Biol. (2003) [Pubmed]

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