Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.celrep.2020.108574
Title: | Zinc Finger Protein SALL4 Functions through an AT-Rich Motif to Regulate Gene Expression | Authors: | Kong, Nikki R. Bassal, Mahmoud A. Tan, Hong Kee Kurland, Jesse, V Yong, Kol Jia Young, John J. Yang, Yang Li, Fudong Lee, Jonathan D. Liu, Yue Wu, Chan-Shuo Stein, Alicia Luo, Hongbo R. Silberstein, Leslie E. Bulyk, Martha L. Tenen, Daniel G. Chai, Li |
Keywords: | CUT&RUN heterochromatin KDM liver cancer protein binding microarray SALL4 transcription |
Issue Date: | 1-Jan-2021 | Publisher: | Elsevier B.V. | Citation: | Kong, Nikki R., Bassal, Mahmoud A., Tan, Hong Kee, Kurland, Jesse, V, Yong, Kol Jia, Young, John J., Yang, Yang, Li, Fudong, Lee, Jonathan D., Liu, Yue, Wu, Chan-Shuo, Stein, Alicia, Luo, Hongbo R., Silberstein, Leslie E., Bulyk, Martha L., Tenen, Daniel G., Chai, Li (2021-01-01). Zinc Finger Protein SALL4 Functions through an AT-Rich Motif to Regulate Gene Expression. Cell Reports 34 (1) : 108574. ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2020.108574 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International | Abstract: | The zinc finger transcription factor SALL4 is highly expressed in embryonic stem cells, downregulated in most adult tissues, but reactivated in many aggressive cancers. This unique expression pattern makes SALL4 an attractive therapeutic target. However, whether SALL4 binds DNA directly to regulate gene expression is unclear, and many of its targets in cancer cells remain elusive. Here, through an unbiased screen of protein binding microarray (PBM) and cleavage under targets and release using nuclease (CUT&RUN) experiments, we identify and validate the DNA binding domain of SALL4 and its consensus binding sequence. Combined with RNA sequencing (RNA-seq) analyses after SALL4 knockdown, we discover hundreds of new SALL4 target genes that it directly regulates in aggressive liver cancer cells, including genes encoding a family of histone 3 lysine 9-specific demethylases (KDMs). Taken together, these results elucidate the mechanism of SALL4 DNA binding and reveal pathways and molecules to target in SALL4-dependent tumors. © 2020 The Author(s)In this paper, Kong et al. elucidate the DNA binding mechanisms of the transcription factor SALL4 and an epigenetic pathway that it regulates. Due to its important role in driving aggressive cancers, better understanding of SALL4 function will lead to strategies to target this protein in cancer. © 2020 The Author(s) | Source Title: | Cell Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/233809 | ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2020.108574 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International |
Appears in Collections: | Elements Staff Publications |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1016_j_celrep_2020_108574.pdf | 5.23 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License