title: Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor.
abstract: Maintaining quiescent cells in G0 phase is achieved in part through the multiprotein subunit complex known as DREAM, and in human cell lines the transcription factor E2F4 directs this complex to its cell cycle targets. We found that E2F4 binds a highly overlapping set of human genes among three diverse primary tissues and an asynchronous cell line, which suggests that tissue-specific binding partners and chromatin structure have minimal influence on E2F4 targeting. To investigate the conservation of these transcription factor binding events, we identified the mouse genes bound by E2f4 in seven primary mouse tissues and a cell line. E2f4 bound a set of mouse genes that was common among mouse tissues, but largely distinct from the genes bound in human. The evolutionarily conserved set of E2F4 bound genes is highly enriched for functionally relevant regulatory interactions important for maintaining cellular quiescence. In contrast, we found minimal mRNA expression perturbations in this core set of E2f4 bound genes in the liver, kidney, and testes of E2f4 null mice. Thus, the regulatory mechanisms maintaining quiescence are robust even to complete loss of conserved transcription factor binding events.
authors.affiliation: Cancer Research UK-Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Conboy
authors.forename: Christiana
authors.initials: C
authors.lastname: Spyrou
authors.forename: Natalie P
authors.initials: NP
authors.lastname: Thorne
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Wade
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Barbosa-Morais
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Arindam
authors.initials: A
authors.lastname: Bhattacharjee
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Lees
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017124:Conserved Sequence; D050704:E2F4 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050704:E2F4 Transcription Factor; D014157:Transcription Factors