A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence. Lu, B., Klingbeil, O., Tarumoto, Y., Somerville, T., Huang, Y., Wei, Y., Wai, D., Low, J., Milazzo, J., Wu, X., Shi, J., & Vakoc, C. Cancer Cell, 34(6):970-981.e8, 2018. doi abstract bibtex 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.SCOPUS_ABS_SEPARATORLu et al. show that MLL-rearranged leukemia is addicted to the transcription factor ZFP64 due to direct regulation of MLL by ZFP64. The MLL promoter has an unusually high number of ZFP64 binding motifs and is the most enriched location of ZFP64 occupancy in the human genome.
@article{
title = {A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence},
type = {article},
year = {2018},
pages = {970-981.e8},
volume = {34},
id = {cdabe452-f0bc-3b9a-a76b-3912d34763ca},
created = {2023-01-10T01:44:14.809Z},
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last_modified = {2023-01-10T01:44:14.809Z},
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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.SCOPUS_ABS_SEPARATORLu et al. show that MLL-rearranged leukemia is addicted to the transcription factor ZFP64 due to direct regulation of MLL by ZFP64. The MLL promoter has an unusually high number of ZFP64 binding motifs and is the most enriched location of ZFP64 occupancy in the human genome.},
bibtype = {article},
author = {Lu, B. and Klingbeil, O. and Tarumoto, Y. and Somerville, T.D.D. and Huang, Y.-H. and Wei, Y. and Wai, D.C. and Low, J.K.K. and Milazzo, J.P. and Wu, X.S. and Shi, J. and Vakoc, C.R.},
doi = {10.1016/j.ccell.2018.10.015},
journal = {Cancer Cell},
number = {6}
}
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