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

Kang, Keunsoo; Choi, Yoonjung; Kim, Hoo Hyun; Yoo, Kyung Hyun; Yu, Sungryul

doi:10.3390/ijms21176141

Open AccessArticle

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

by

Keunsoo Kang

^1,*,†,

Yoonjung Choi

^2,†,

Hoo Hyun Kim

¹,

Kyung Hyun Yoo

^3,4

and

Sungryul Yu

^5,*

¹

Department of Microbiology, College of Science & Technology, Dankook University, Cheonan 31116, Korea

²

Deargen Inc., Daejeon 34051, Korea

³

Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea

⁴

Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea

⁵

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

Submission 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”)

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Abstract

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.

Keywords: FOXM1; NFY; ChIP-seq; cell cycle; master regulator; breast cancer; MCF-7

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MDPI and ACS Style

Kang, K.; Choi, Y.; Kim, H.H.; Yoo, K.H.; Yu, S. 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. Int. J. Mol. Sci. 2020, 21, 6141. https://doi.org/10.3390/ijms21176141

AMA Style

Kang K, Choi Y, Kim HH, Yoo KH, Yu S. 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. International Journal of Molecular Sciences. 2020; 21(17):6141. https://doi.org/10.3390/ijms21176141

Chicago/Turabian Style

Kang, Keunsoo, Yoonjung Choi, Hoo Hyun Kim, Kyung Hyun Yoo, and Sungryul Yu. 2020. "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" International Journal of Molecular Sciences 21, no. 17: 6141. https://doi.org/10.3390/ijms21176141

APA Style

Kang, K., Choi, Y., Kim, H. H., Yoo, K. H., & Yu, S. (2020). 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. International Journal of Molecular Sciences, 21(17), 6141. https://doi.org/10.3390/ijms21176141

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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

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