Cited by 181Genomics and Chromatin DynamicsCancer-related Molecular PathwaysGene Regulatory Network Analysis

Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors

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Grant, Gavin D., Brooks, Lionel, Zhang, Xiaoyang, Mahoney, J. Matthew, Martyanov, Viktor, Wood, Tammara A., Sherlock, Gavin, Cheng, Chao +1 more·2013·Molecular Biology of the Cell

Abstract

We identify the cell cycle-regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle-regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle-regulated genes. FOXM1 is bound to cell cycle-regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle-regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle.

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Authors
Grant, G. D., Brooks, L., Zhang, X., Mahoney, J. M., Martyanov, V., Wood, T. A., Sherlock, G., Cheng, C., & Whitfield, M. L.
Affiliations
  • Dartmouth College (US)
  • Stanford Medicine (US)
Corresponding author
Whitfield, Michael L.
Venue
Molecular Biology of the Cell
Published
2013-12
Volume
24
Issue
23
Pages
3634-3650
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2102123859
Cited by
179
References
92
Citations by year
2026: 5 · 2025: 11 · 2024: 13 · 2023: 6 · 2022: 10 · 2021: 21 · 2020: 19 · 2019: 17 · 2018: 14 · 2017: 20 · 2016: 17 · 2015: 14 · 2014: 12
FWCI
6.42
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Foundation for the National Institutes of Health
  • V Foundation for Cancer Research
  • National Human Genome Research Institute (R01HG004499)
  • National Cancer Institute (R25CA134286, R01CA130795)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
cell cycle-regulated genes, periodic gene expression, FOXM1, E2F transcription factors, G2/M phase, S phase, osteosarcoma, U2OS cells, transcriptional regulation, DREAM complex, GABPA, E2F1, E2F4, E2F6, promoter activation
MeSH terms
Forkhead Box Protein M1, Cell Cycle, Multigene Family, HeLa Cells, Humans, Protein Binding, RNA, Messenger, Time Factors, Transcription, Genetic, Protein Biosynthesis, Gene Expression Regulation, Neoplastic, Genes, cdc, Gene Expression Profiling, Chromatin Immunoprecipitation, E2F Transcription Factors, Forkhead Transcription Factors

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