A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence

Lu, B., Klingbeil, O., Tarumoto, Y., Somerville, T. D. D., Huang, Y. H., Wei, Y., Wai, D. C., Low, J. K. K., Milazzo, J. P., Wu, X. S., Cao, Z., Yan, X., Demerdash, O. E., Huang, G., Mackay, J. P., Kinney, J. B., Shi, J., Vakoc, C. R. (November 2018) A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence. Cancer Cell, 34 (6). pp. 970-981. ISSN 1535-6108

URL: https://www.ncbi.nlm.nih.gov/pubmed/30503706
DOI: 10.1016/j.ccell.2018.10.015

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.

Item Type: Paper
Additional Information: 1878-3686 Lu, Bin Klingbeil, Olaf Tarumoto, Yusuke Somerville, Tim D D Huang, Yu-Han Wei, Yiliang Wai, Dorothy C Low, Jason K K Milazzo, Joseph P Wu, Xiaoli S Cao, Zhendong Yan, Xiaomei Demerdash, Osama E Huang, Gang Mackay, Joel P Kinney, Justin B Shi, Junwei Vakoc, Christopher R Journal Article United States Cancer Cell. 2018 Nov 15. pii: S1535-6108(18)30481-1. doi: 10.1016/j.ccell.2018.10.015.
Uncontrolled Keywords: CRISPR screen Mll Zfp64 addiction leukemia motif oncogene promoter
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA translocation
diseases & disorders > cancer > cancer types > leukemia
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > promoter
CSHL Authors:
Communities: CSHL labs > Kinney lab
CSHL labs > Vakoc lab
Depositing User: Matthew Dunn
Date: 15 November 2018
Date Deposited: 20 Dec 2018 17:47
Last Modified: 07 Jan 2019 16:16
URI: http://repository.cshl.edu/id/eprint/37512

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