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Updated: Jul 14, 2026
12:19
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes
Larisa Litovchick1, Subhashini Sadasivam, Laurence Florens
1Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Molecular Cell
|May 29, 2007
Summary
Researchers discovered a conserved protein complex, DREAM, involving p130 and E2F4. This complex represses cell cycle genes during quiescence, offering new insights into gene regulation.
Area of Science:
- Molecular Biology
- Cell Cycle Regulation
- Gene Expression
Background:
- The Retinoblastoma (RB) protein family regulates gene expression, but its precise mechanisms, especially in quiescence, remain unclear.
- RB-mediated repression involves E2F target genes and is conserved across species, with homologs in Drosophila and C. elegans.
Purpose of the Study:
- To identify and characterize the mammalian protein complex responsible for RB-family-mediated repression of E2F target genes in quiescent cells.
- To elucidate the composition and function of this complex in regulating cell cycle-dependent gene expression.
Main Methods:
- Integrated proteomics, genomics, and bioinformatic analyses were employed.
- Chromatin immunoprecipitation (ChIP) and mass spectrometry were used to identify protein interactions and DNA binding.
- Analysis of protein complex dynamics during the cell cycle (G0 vs. S phase).
Main Results:
- A novel p130-containing complex, termed DREAM (DP, RB-like, E2F, and MuvB), was identified, comprising mammalian homologs of C. elegans synMuvB proteins (LIN-9, LIN-37, LIN-52, LIN-54, LIN-53/RBBP4).
- The DREAM complex binds to over 800 human promoters in the G0 (quiescent) phase and is essential for repressing E2F target genes.
- During S phase, MuvB proteins dissociate from p130, form a distinct submodule, and bind to MYB, indicating dynamic regulation.
Conclusions:
- The DREAM complex, containing p130 and E2F4 but not pRB, is an evolutionarily conserved regulator of cell cycle-dependent gene repression in quiescence.
- This discovery provides a mechanistic link between RB family proteins, E2F, and MuvB homologs in controlling cell cycle exit and maintenance.
- The findings offer new targets for understanding and potentially manipulating cell cycle control in various biological contexts.
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