Article
- The EMBO Journal (2008) 27, 2839 - 2850
- doi:10.1038/emboj.2008.214
Published online: 16 October 2008
Subject Categories:
CTCF regulates cell cycle progression of 
T cells in the thymus
Helen Heath1,ab, Claudia Ribeiro de Almeida2,3,b, Frank Sleutels1, Gemma Dingjan2, Suzanne van de Nobelen1, Iris Jonkers4, Kam-Wing Ling2, Joost Gribnau4, Rainer Renkawitz5, Frank Grosveld1, Rudi W Hendriks2,3 and Niels Galjart1
- Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
- Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
- Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands
- Department of Reproduction and Development, Erasmus MC, Rotterdam, The Netherlands
- Institute for Genetics, Justus-Liebig-Universitaet Giessen, Giessen, Germany
Correspondence to:
Niels Galjart, Department of Cell Biology and Genetics, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 10 7043163; Fax: +31 10 7044743; E-mail: n.galjart@erasmusmc.nl
Rudi W Hendriks, Department of Pulmonary Medicine, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 10 7043700; Fax: +31 10 7044728; E-mail: r.hendriks@erasmusmc.nl
aPresent address: Developmental Signalling Laboratory, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
bThese authors contributed equally to this work
Received 5 May 2008; Accepted 19 September 2008
Abstract
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 
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 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.
Keywords:
- cell cycle,
- chromatin,
- CTCF,
- nuclear organization,
- T cells
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