TY - JOUR
T1 - Cell cycle genes are the evolutionarily conserved targets of the E2F4 transcription factor
AU - Conboy, Caitlin M.
AU - Spyrou, Christiana
AU - Thorne, Natalie P.
AU - Wade, Elizabeth J.
AU - Barbosa-Morais, Nuno L.
AU - Wilson, Michael D.
AU - Bhattacharjee, Arindam
AU - Young, Richard A.
AU - Tavaré, Simon
AU - Lees, Jacqueline A.
AU - Odom, Duncan T.
PY - 2007/10/24
Y1 - 2007/10/24
N2 - 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. Copyright:
AB - 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. Copyright:
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U2 - 10.1371/journal.pone.0001061
DO - 10.1371/journal.pone.0001061
M3 - Article
C2 - 17957245
AN - SCOPUS:42349088542
SN - 1932-6203
VL - 2
JO - PloS one
JF - PloS one
IS - 10
M1 - e1061
ER -