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Publication : CTCF regulates cell cycle progression of alphabeta T cells in the thymus.

First Author  Heath H Year  2008
Journal  EMBO J Volume  27
Issue  21 Pages  2839-50
PubMed ID  18923423 Mgi Jnum  J:143271
Mgi Id  MGI:3826307 Doi  10.1038/emboj.2008.214
Citation  Heath H, et al. (2008) CTCF regulates cell cycle progression of alphabeta T cells in the thymus. EMBO J 27(21):2839-50
abstractText  The 11-zinc finger protein CCCTC-binding factor (CTCF) is a highly conserved protein, involved in imprinting, long-range chromatin interactions and transcription. To investigate its function in vivo, we generated mice with a conditional Ctcf knockout allele. Consistent with a previous report, we find that ubiquitous ablation of the Ctcf gene results in early embryonic lethality. Tissue-specific inactivation of CTCF in thymocytes specifically hampers the differentiation of alphabeta T cells and causes accumulation of late double-negative and immature single-positive cells in the thymus of mice. These cells are normally large and actively cycling, and contain elevated amounts of CTCF. In Ctcf knockout animals, however, these cells are small and blocked in the cell cycle due to increased expression of the cyclin-CDK inhibitors p21 and p27. Taken together, our results show that CTCF is required in a dose-dependent manner and is involved in cell cycle progression of alphabeta T cells in the thymus. We propose that CTCF positively regulates cell growth in rapidly dividing thymocytes so that appropriate number of cells are generated before positive and negative selection in the thymus.
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