| 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
|
| リソース情報 |
| ヒト・動物細胞 |
K-1.fl(RCB0559) |
