論文 - 詳細
| RRC ID | 61421 |
|---|---|
| 著者 | Oka M, Mura S, Yamada K, Sangel P, Hirata S, Maehara K, Kawakami K, Tachibana T, Ohkawa Y, Kimura H, Yoneda Y. |
| タイトル | Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes. |
| ジャーナル | Elife |
| Abstract |
The nucleoporin Nup98 is frequently rearranged to form leukemogenic Nup98-fusion proteins with various partners. However, their function remains largely elusive. Here, we show that Nup98-HoxA9, a fusion between Nup98 and the homeobox transcription factor HoxA9, forms nuclear aggregates that frequently associate with facultative heterochromatin. We demonstrate that stable expression of Nup98-HoxA9 in mouse embryonic stem cells selectively induces the expression of Hox cluster genes. Genome-wide binding site analysis revealed that Nup98-HoxA9 is preferentially targeted and accumulated at Hox cluster regions where the export factor Crm1 is originally prebound. In addition, leptomycin B, an inhibitor of Crm1, disassembled nuclear Nup98-HoxA9 dots, resulting in the loss of chromatin binding of Nup98-HoxA9 and Nup98-HoxA9-mediated activation of Hox genes. Collectively, our results indicate that highly selective targeting of Nup98-fusion proteins to Hox cluster regions via prebound Crm1 induces the formation of higher order chromatin structures that causes aberrant Hox gene regulation. |
| 巻・号 | 5 |
| ページ | e09540 |
| 公開日 | 2016-1-7 |
| DOI | 10.7554/eLife.09540 |
| PII | e09540 |
| PMID | 26740045 |
| PMC | PMC4718815 |
| MeSH | Animals Cell Line Chromatin / metabolism* Embryonic Stem Cells / metabolism Gene Expression Regulation* Homeodomain Proteins / metabolism* Humans Karyopherins / metabolism* Mice Nuclear Pore Complex Proteins / metabolism* Protein Binding Receptors, Cytoplasmic and Nuclear / metabolism* |
| IF | 7.08 |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | K-1.fl(RCB0559) |