TY - JOUR TI - Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes AU - Oka, Masahiro AU - Mura, Sonoko AU - Yamada, Kohji AU - Sangel, Percival AU - Hirata, Saki AU - Maehara, Kazumitsu AU - Kawakami, Koichi AU - Tachibana, Taro AU - Ohkawa, Yasuyuki AU - Kimura, Hiroshi AU - Yoneda, Yoshihiro A2 - Weis, Karsten VL - 5 PY - 2016 DA - 2016/01/07 SP - e09540 C1 - eLife 2016;5:e09540 DO - 10.7554/eLife.09540 UR - https://doi.org/10.7554/eLife.09540 AB - 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. KW - Nucleoporin KW - Nup98 KW - Crm1 KW - Leukemia KW - Hox KW - Chromatin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -