501. Tissue-specific inactivation of HAT cofactor TRRAP reveals its essential role in B cells.
- Author
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Leduc C, Chemin G, Puget N, Sawan C, Moutahir M, Herceg Z, and Khamlichi AA
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Animals, Apoptosis, B-Lymphocytes cytology, Cell Proliferation, Immunoglobulin Class Switching, Mice, Mutant Strains, Nuclear Proteins metabolism, Organ Specificity, Adaptor Proteins, Signal Transducing genetics, B-Lymphocytes metabolism, Histone Acetyltransferases metabolism, Nuclear Proteins genetics
- Abstract
The transformation/transcription domain-associated protein (TRRAP) is a common component of many histone acetyltransferase (HAT) complexes. Targeted-deletion of the Trrap gene led to early embryonic lethality and revealed a critical function of TRRAP in cell proliferation. Here, we investigate the function of TRRAP in murine B cells. To this end, we ablated Trrap gene in a B cell-restricted manner and studied its impact on B-cell development and proliferation, a pre-requisite for class switch recombination (CSR), the process that allows IgM-expressing B lymphocytes to switch to the expression of IgG, IgE, or IgA isotypes. We show that TRRAP deficiency impairs B-cell development but does not directly affect CSR. Instead, cells induced to proliferate undergo apoptosis. Our findings demonstrate a central and general role of TRRAP in cell proliferation.
- Published
- 2014
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