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CTCF regulates cell cycle progression of αβ T cells in the thymus
Author(s) -
Heath Helen,
de Almeida Claudia Ribeiro,
Sleutels Frank,
Dingjan Gemma,
van de Nobelen Suzanne,
Jonkers Iris,
Ling KamWing,
Gribnau Joost,
Renkawitz Rainer,
Grosveld Frank,
Hendriks Rudi W,
Galjart Niels
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.214
Subject(s) - ctcf , biology , chromatin , cell cycle , microbiology and biotechnology , embryonic stem cell , transcription factor , zinc finger , cell , genetics , gene , enhancer
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 αβ 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 αβ 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.