TY - JOUR TI - Chromatin-bound CRM1 recruits SET-Nup214 and NPM1c onto HOX clusters causing aberrant HOX expression in leukemia cells AU - Oka, Masahiro AU - Mura, Sonoko AU - Otani, Mayumi AU - Miyamoto, Yoichi AU - Nogami, Jumpei AU - Maehara, Kazumitsu AU - Harada, Akihito AU - Tachibana, Taro AU - Yoneda, Yoshihiro AU - Ohkawa, Yasuyuki A2 - Weis, Karsten A2 - Manley, James L A2 - Doye, Valerie VL - 8 PY - 2019 DA - 2019/11/22 SP - e46667 C1 - eLife 2019;8:e46667 DO - 10.7554/eLife.46667 UR - https://doi.org/10.7554/eLife.46667 AB - We previously demonstrated that CRM1, a major nuclear export factor, accumulates at Hox cluster regions to recruit nucleoporin-fusion protein Nup98HoxA9, resulting in robust activation of Hox genes (Oka et al., 2016). However, whether this phenomenon is general to other leukemogenic proteins remains unknown. Here, we show that two other leukemogenic proteins, nucleoporin-fusion SET-Nup214 and the NPM1 mutant, NPM1c, which contains a nuclear export signal (NES) at its C-terminus and is one of the most frequent mutations in acute myeloid leukemia, are recruited to the HOX cluster region via chromatin-bound CRM1, leading to HOX gene activation in human leukemia cells. Furthermore, we demonstrate that this mechanism is highly sensitive to a CRM1 inhibitor in leukemia cell line. Together, these findings indicate that CRM1 acts as a key molecule that connects leukemogenic proteins to aberrant HOX gene regulation either via nucleoporin-CRM1 interaction (for SET-Nup214) or NES-CRM1 interaction (for NPM1c). KW - CRM1 KW - NPM1c KW - SET-Nup214 KW - HOX cluster KW - nucleoporin KW - leukemia JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -