生物
染色质免疫沉淀
融合蛋白
染色质
融合基因
基因
免疫沉淀
遗传学
分子生物学
基因表达
癌症研究
发起人
重组DNA
作者
Haiming Xu,Daria G. Valerio,Meghan E. Eisold,Amit Sinha,Richard P. Koche,Wenhuo Hu,Chun‐Wei Chen,S. Haihua Chu,Gerard L. Brien,Christopher Y. Park,James J. Hsieh,Patricia Ernst,Scott A. Armstrong
出处
期刊:Cancer Cell
[Elsevier]
日期:2016-11-23
卷期号:30 (6): 863-878
被引量:126
标识
DOI:10.1016/j.ccell.2016.10.019
摘要
The nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in multiple hematopoietic malignancies. Here, we demonstrate that NUP98 fusion proteins, including NUP98-HOXA9 (NHA9), NUP98-HOXD13 (NHD13), NUP98-NSD1, NUP98-PHF23, and NUP98-TOP1 physically interact with mixed lineage leukemia 1 (MLL1) and the non-specific lethal (NSL) histone-modifying complexes. Chromatin immunoprecipitation sequencing illustrates that NHA9 and MLL1 co-localize on chromatin and are found associated with Hox gene promoter regions. Furthermore, MLL1 is required for the proliferation of NHA9 cells in vitro and in vivo. Inactivation of MLL1 leads to decreased expression of genes bound by NHA9 and MLL1 and reverses a gene expression signature found in NUP98-rearranged human leukemias. Our data reveal a molecular dependency on MLL1 function in NUP98-fusion-driven leukemogenesis.
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