Predicting FOXM1-Mediated Gene Regulation through the Analysis of Genome-Wide FOXM1 Binding Sites in MCF-7, K562, SK-N-SH, GM12878 and ECC-1 Cell Lines
Department of Microbiology, College of Science & Technology, Dankook University, Cheonan 31116, Korea
Deargen Inc., Daejeon 34051, Korea
Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea
Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea
Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Int. J. Mol. Sci. 2020, 21(17), 6141; https://doi.org/10.3390/ijms21176141
Received: 22 June 2020 / Revised: 16 August 2020 / Accepted: 24 August 2020 / Published: 26 August 2020
(This article belongs to the Special Issue Molecular Mechanisms of Gene Expression: “Bioinformatics of Gene Regulations and Structure”)
Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. However, the mechanism by which FOXM1 controls the common gene set in different cellular contexts is unclear. In this study, a comprehensive meta-analysis of genome-wide FOXM1 binding sites in ECC-1, GM12878, K562, MCF-7, and SK-N-SH cell lines was conducted to predict FOXM1-driven gene regulation. Consistent with previous studies, different TF binding motifs were identified at FOXM1 binding sites, while the NFY binding motif was found at 81% of common FOXM1 binding sites in promoters of cell cycle-related genes. The results indicated that FOXM1 might control the gene set through interaction with the NFY proteins, while cell type-specific genes were predicted to be regulated by enhancers with FOXM1 and cell type-specific TFs. We also found that the high expression level of FOXM1 was significantly associated with poor prognosis in nine types of cancer. Overall, these results suggest that FOXM1 is predicted to function as a master regulator of the cell cycle through the interaction of NFY-family proteins, and therefore the inhibition of FOXM1 could be an attractive strategy for cancer therapy.