Regulation of early T cell development by the PHD finger of histone lysine methyltransferase ASH1.
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 alphabeta T cells.
Tanaka
Yujiro
Y
Genome Structure and Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113-8610, Japan.
Nakayama
Yasuhiro
Y
Taniguchi
Masaru
M
Kioussis
Dimitris
D
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000201:enzymology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins; C499317:Ascl1 protein, mouse; C097899:homeobox protein HOXA9; C064658:RAG-1 protein; C484389:Hdac1 protein, mouse