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Updated: Apr 3, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes
Martin Fischer1, Marianne Quaas1, Lydia Steiner2
1Molecular Oncology, Medical School, University of Leipzig, Leipzig, Germany.
Abstract:
The tumor suppressor p53 functions predominantly as a transcription factor by activating and downregulating gene expression, leading to cell cycle arrest or apoptosis. p53 was shown to indirectly repress transcription of the CCNB2, KIF23 and PLK4 cell cycle genes through the recently discovered p53-p21-DREAM-CDE/CHR pathway. However, it remained unclear whether this pathway is commonly used. Here, we identify genes regulated by p53 through this pathway in a genome-wide computational approach. The bioinformatic analysis is based on genome-wide DREAM complex binding data, p53-depedent mRNA expression data and a genome-wide definition of phylogenetically conserved CHR promoter elements. We find 210 target genes that are expected to be regulated by the p53-p21-DREAM-CDE/CHR pathway. The target gene list was verified by detailed analysis of p53-dependent repression of the cell cycle genes B-MYB (MYBL2), BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18 and RAD54L. Most of the 210 target genes are essential regulators of G2 phase and mitosis. Thus, downregulation of these genes through the p53-p21-DREAM-CDE/CHR pathway appears to be a principal mechanism for G2/M cell cycle arrest by p53.
Insights
The tumor suppressor p53 regulates cell cycle genes via the p53-p21-DREAM-CDE/CHR pathway. This pathway is a key mechanism for p53-induced G2/M cell cycle arrest.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The tumor suppressor p53 is a transcription factor controlling cell cycle arrest and apoptosis.
- p53 indirectly represses cell cycle genes (e.g., CCNB2, KIF23, PLK4) via the p53-p21-DREAM-CDE/CHR pathway.
- The prevalence of this regulatory pathway remained largely uncharacterized.
Purpose of the Study:
- To identify genes regulated by p53 through the p53-p21-DREAM-CDE/CHR pathway on a genome-wide scale.
- To determine if this pathway is a principal mechanism for p53-mediated G2/M cell cycle arrest.
Main Methods:
- Genome-wide computational analysis integrating DREAM complex binding data, p53-dependent mRNA expression data, and conserved CHR promoter elements.
- Bioinformatic identification of potential target genes.
- Experimental validation of p53-dependent repression for specific cell cycle genes (e.g., MYBL2, BUB1, CCNA2).
Main Results:
- Identified 210 target genes regulated by the p53-p21-DREAM-CDE/CHR pathway.
- Confirmed p53-dependent repression of key cell cycle genes including MYBL2, BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18, and RAD54L.
- The majority of the 210 identified genes are critical for G2 phase and mitosis regulation.
Conclusions:
- The p53-p21-DREAM-CDE/CHR pathway is a significant mechanism by which p53 regulates gene expression.
- Downregulation of essential G2/M regulators via this pathway is a principal mechanism for p53-induced G2/M cell cycle arrest.
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