Regulation of early T cell development by the PHD finger of histone lysine methyltransferase ASH1
- Genome Structure and Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113-8610 (Japan)
- Department of Genetics, Yale University School of Medicine, 300 Cedar St., New Haven, CT 06510 (United States)
- Department of Developmental Immunology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan)
- Department of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom)
We have previously isolated a mammalian homologue of Drosophila discsabsent, small, orhomeotic-1 (ash1) from the murine thymus, and recently shown that its SET domain methylates histone H3 lysine 36 (K36). Expression of ASH1 has been reported to be increased in NOD thymocytes in a BDC2.5 clonotype background, but its function in T cell development has remained elusive. Here we report that the ash1 gene is expressed at high levels in thymocytes of mice deficient for rag1 or tcra genes. ASH1 proteins are present at peri-nuclei and as nuclear speckles in thymocytes. Some of the nuclear ASH1 co-localize with RAG2. Expression of the evolutionarily conserved PHD finger of ASH1 impairs T cell development at the DP stage, and causes increased transcription from the HoxA9 promoter in vitro. Moreover, the C-terminal part of ASH1 interacts with HDAC1 repression complexes, suggesting that the PHD finger of ASH1 may be involved in down-regulation of genes for normal development of {alpha}{beta} T cells.
- OSTI ID:
- 21043580
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 365, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.10.159; PII: S0006-291X(07)02320-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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