A single cell cycle genes homology region (CHR) controls cell cycle-dependent transcription of the cdc25C phosphatase gene and is able to cooperate with E2F or Sp1/3 sites.
The cdc25C phosphatase participates in regulating transition from the G2 phase of the cell cycle to mitosis by dephosphorylating cyclin-dependent kinase 1. The tumor suppressor p53 down-regulates expression of cdc25C as part of G2/M checkpoint control. Transcription of cdc25C oscillates during the cell cycle with no expression in resting cells and maximum transcription in G2. We had identified earlier a new mechanism of cell cycle-dependent transcription that is regulated by a cell cycle-dependent element (CDE) in conjunction with a cell cycle genes homology region (CHR). The human cdc25C gene was the first example. CDE/CHR tandem elements have since been found in promoters of many cell cycle genes. Here we show that the mouse cdc25C gene is regulated by a CHR but does not hold a CDE. Therefore, it is the first identified gene with CHR-dependent transcriptional regulation during the cell cycle not relying on a CDE located upstream of it. The CHR leads to repression of cdc25C transcription early in the cell cycle and directs a release of this repression in G2. Furthermore, we find that this CHR can cooperate in cell cycle-dependent transcription with elements placed directly upstream of it binding E2F, Sp1 or Sp3 transcription factors.
Haugwitz
Ulrike
U
Department of Internal Medicine II, University of Leipzig, Max Bürger Research Center, Johannisallee 30, D-04103 Leipzig, Germany.
Wasner
Mark
M
Wiedmann
Marcus
M
Spiesbach
Katja
K
Rother
Karen
K
Mössner
Joachim
J
Engeland
Kurt
K
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D050684:E2F Transcription Factors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics*
D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C402244:nuclear factor Y; D051705:Sp3 Transcription Factor; C517009:CDC25C protein, human; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases