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

Mol Biol Cell. 2013 Dec;24(23):3634-50. doi: 10.1091/mbc.E13-05-0264. Epub 2013 Oct 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Chromatin Immunoprecipitation
  • E2F Transcription Factors / metabolism*
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, cdc*
  • HeLa Cells
  • Humans
  • Multigene Family
  • Protein Binding / genetics
  • Protein Biosynthesis / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Transcription, Genetic

Substances

  • E2F Transcription Factors
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • RNA, Messenger