| Literature DB >> 30503706 |
Bin Lu1, Olaf Klingbeil1, Yusuke Tarumoto1, Tim D D Somerville1, Yu-Han Huang1, Yiliang Wei1, Dorothy C Wai2, Jason K K Low2, Joseph P Milazzo1, Xiaoli S Wu1, Zhendong Cao3, Xiaomei Yan4, Osama E Demerdash1, Gang Huang4, Joel P Mackay2, Justin B Kinney1, Junwei Shi5, Christopher R Vakoc6.
Abstract
The Mixed Lineage Leukemia gene (MLL) is altered in leukemia by chromosomal translocations to produce oncoproteins composed of the MLL N-terminus fused to the C-terminus of a partner protein. Here, we used domain-focused CRISPR screening to identify ZFP64 as an essential transcription factor in MLL-rearranged leukemia. We show that the critical function of ZFP64 in leukemia is to maintain MLL expression via binding to the MLL promoter, which is the most enriched location of ZFP64 occupancy in the human genome. The specificity of ZFP64 for MLL is accounted for by an exceptional density of ZFP64 motifs embedded within the MLL promoter. These findings demonstrate how a sequence anomaly of an oncogene promoter can impose a transcriptional addiction in cancer.Entities:
Keywords: CRISPR screen; MLL; ZFP64; addiction; leukemia; motif; oncogene; promoter
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Year: 2018 PMID： 30503706 PMCID： PMC6554023 DOI： 10.1016/j.ccell.2018.10.015
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585