E2Fs regulate adipocyte differentiation.
When preadipocytes reenter the cell cycle, PPAR gamma expression is induced, coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. We show here that E2F1 induces PPAR gamma transcription during clonal expansion, whereas E2F4 represses PPARg amma expression during terminal adipocyte differentiation. Using a combination of in vivo experiments with knockout and chimeric animals and in vitro experiments, we demonstrate that the absence of E2F1 impairs, whereas depletion of E2F4 stimulates, adipogenesis. E2Fs hence represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPAR gamma expression. This underscores the complex role of the E2F protein family in the control of both cell proliferation and differentiation.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163, F-67404 Illkirch cedex, C.U. de, Strasbourg, France.
Lluis
L
Fajas
Rebecca L
RL
Landsberg
Yolande
Y
Huss-Garcia
Claude
C
Sardet
Jacqueline A
JA
Lees
Johan
J
Auwerx
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; C493754:E2f1 protein, mouse; C490840:E2f3 protein, mouse; C493763:E2f4 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors