A common set of gene regulatory networks links metabolism and growth inhibition

Hugh Cam, Egle Balciunaite, Alexandre Blais, Alexander Spektor, Richard C. Scarpulla, Richard Young, Yuval Kluger, Brian David Dynlacht*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

244 Scopus citations

Abstract

Using genome-wide analysis of transcription factor occupancy, we investigated the mechanisms underlying three mammalian growth arrest pathways that require the pRB tumor suppressor family. We found that p130 and E2F4 cooperatively repress a common set of genes under each growth arrest condition and showed that growth arrest is achieved through repression of a core set of genes involved not only in cell cycle control but also mitochondrial biogenesis and metabolism. Motif-finding algorithms predicted the existence of nuclear respiratory factor-1 (NRF1) binding sites in E2F target promoters, and genome-wide factor binding analysis confirmed our predictions. We showed that NRF1, a factor known to regulate expression of genes involved in mitochondrial function, is a coregulator of a large number of E2F target genes. Our studies provide insights into E2F regulatory circuitry, suggest how factor occupancy can predict the expression signature of a given target gene, and reveal pathways deregulated in human tumors.

Original languageEnglish (US)
Pages (from-to)399-411
Number of pages13
JournalMolecular cell
Volume16
Issue number3
DOIs
StatePublished - Nov 5 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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