論文 - 詳細
| RRC ID | 37098 |
|---|---|
| 著者 | Mizutani S, Yoshida T, Zhao X, Nimer SD, Taniwaki M, Okuda T. |
| タイトル | Loss of RUNX1/AML1 arginine-methylation impairs peripheral T cell homeostasis. |
| ジャーナル | Br J Haematol |
| Abstract |
RUNX1 (previously termed AML1) is a frequent target of human leukaemia-associated gene aberrations, and it encodes the DNA-binding subunit of the Core-Binding Factor transcription factor complex. RUNX1 expression is essential for the initiation of definitive haematopoiesis, for steady-state thrombopoiesis, and for normal lymphocytes development. Recent studies revealed that protein arginine methyltransferase 1 (PRMT1), which accounts for the majority of the type I PRMT activity in cells, methylates two arginine residues in RUNX1 (R206 and R210), and these modifications inhibit corepressor-binding to RUNX1 thereby enhancing its transcriptional activity. In order to elucidate the biological significance of these methylations, we established novel knock-in mouse lines with non-methylable, double arginine-to-lysine (RTAMR-to-KTAMK) mutations in RUNX1. Homozygous Runx1(KTAMK) (/) (KTAMK) mice are born alive and appear normal during adulthood. However, Runx1(KTAMK) (/) (KTAMK) mice showed a reduction in CD3(+) T lymphoid cells and a decrease in CD4(+) T cells in peripheral lymphoid organs, in comparison to their wild-type littermates, leading to a reduction in the CD4(+) to CD8(+) T-cell ratio. These findings suggest that arginine-methylation of RUNX1 in the RTAMR-motif is dispensable for the development of definitive haematopoiesis and for steady-state platelet production, however this modification affects the role of RUNX1 in the maintenance of the peripheral CD4(+) T-cell population. |
| 巻・号 | 170(6) |
| ページ | 859-73 |
| 公開日 | 2015-9-1 |
| DOI | 10.1111/bjh.13499 |
| PMID | 26010396 |
| PMC | PMC4996932 |
| MeSH | Alleles Amino Acid Motifs Animals Arginine / metabolism* CD4 Lymphocyte Count Core Binding Factor Alpha 2 Subunit / chemistry Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism* Embryonic Stem Cells / metabolism Gene Knock-In Techniques Gene Order Gene Targeting Genetic Vectors / genetics Genotype Germ Cells / metabolism Hematopoiesis* / genetics Humans Methylation Mice Mice, Knockout Mutation Myelopoiesis / genetics Phenotype T-Lymphocytes / metabolism* Transcriptional Activation |
| IF | 5.518 |
| 引用数 | 7 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |