Disruption of E2F signaling suppresses the INK4a-induced proliferative defect in M33-deficient mice.
Polycomb group (Pc-G) proteins associate to form large complexes that repress Hox genes, thereby imposing Hox gene expression pattern required for development. However, Pc-G proteins have a Hox-independent function in controlling cell proliferation. Here we show that embryonic fibroblasts derived from M33-deficient mice are impaired in the progression into the S phase of the cell cycle, as shown by a reduced rate of incorporation of bromodeoxyuridine. These cells have a senescent phenotype, associated to an abnormal accumulation of the cyclin-dependent kinase inhibitor p16INK4a protein. We demonstrate that this defect is bypassed in mutant embryonic fibroblasts expressing a transdominant negative form of the cell cycle controlling transcription factor E2F (E2F-DB). In addition, we show that the polycomb protein M33 controls critical expansion of B- and T-lymphocyte precursors. Together, our results emphasize M33-Polycomb protein function in cell cycle control.
Coré
Nathalie
N
Centre d'Immunologie INSERM/CNRS, Case 906, 13288 Marseille Cedex 9, France.
Joly
Florence
F
Boned
Annie
A
Djabali
Malek
M
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D050684:E2F Transcription Factors; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006854:Hydrocortisone / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
C570426:Cbx2 protein, mouse; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D063150:Polycomb Repressive Complex 1; D006854:Hydrocortisone