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Genome Editing with CompoZr Custom Zinc Finger Nucleases (ZFNs)
Published on: June 14, 2012
Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF
J E Rasko1, E M Klenova, J Leon
1Gene Therapy Research Unit, Centenary Institute of Cancer Medicine and Cell Biology, Newtown New South Wales 2042, Australia.
Cancer Research
|August 17, 2001
Summary
The 11-zinc finger protein CTCF (CCCTC-binding factor) inhibits cell growth and clonogenicity by slowing cell-cycle progression at multiple points, suggesting its role as a tumor suppressor.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The CCCTC-binding factor (CTCF) is an 11-zinc finger protein that binds specific DNA sequences (CTSs).
- CTCF plays diverse roles in gene regulation, including enhancer-blocking (chromatin insulation), gene activation/repression, and formation of hormone-responsive silencers.
Purpose of the Study:
- To investigate the in vivo effects of CTCF on cell growth and proliferation.
- To understand how CTCF integrates its various functions to impact cellular processes.
Main Methods:
- Engineered various expression systems for ectopic CTCF expression in multiple cell types.
- Analyzed cell clonogenicity, cell-cycle profiles, and apoptosis in CTCF-expressing cells.
- Investigated the role of known CTCF targets like MYC and other growth-regulatory genes (e.g., p19ARF).
Main Results:
- Ectopic CTCF expression significantly inhibited cell clonogenicity and caused profound growth retardation without inducing apoptosis.
- CTCF expression slowed cell-cycle progression at multiple points, without altering the overall cell-cycle profile in asynchronous cultures.
- While MYC repression contributes, other CTS-driven genes, such as p19ARF, are also involved in CTCF-mediated growth arrest.
Conclusions:
- CTCF regulates cell-cycle progression at multiple stages.
- CTCF functions as a tumor suppressor, as evidenced by its growth-inhibitory effects on cells.
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