Department of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Genetic Phenomena | Molecular Biology | Neoplasms
Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive X (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.
molecular biology, Ki-67 protein, tumor proliferation marker, chromatin
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 134767; doi: https://doi.org/10.1101/134767. Link to preprint on bioRxiv service.
Now published in Molecular and Cellular Biology doi: 10.1128/MCB.00569-16.
Sun X, Bizhanova A, Matheson TD, Yu J, Zhu LJ, Kaufman PD. (2017). Ki-67 Contributes To Normal Cell Cycle Progression And Inactive X Heterochromatin In p21 Checkpoint-Proficient Human Cells. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/134767. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1534
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