C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis.
CCAAT enhancer binding protein epsilon (C/EBPepsilon) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation. Retinoblastoma (Rb) and E2F1 are critical cell cycle regulators that also have been implicated in several differentiation systems. Here, we demonstrate that C/EBPepsilon interacts with Rb and E2F1 during granulocytic differentiation in NB4 and U937 human myeloid cells and in 32Dcl3 murine myeloid precursor cells. The interaction between C/EBPepsilon and Rb enhances C/EBPepsilon-mediated transcription of myeloid specific genes both in reporter assays and endogenously. The C/EBPepsilon-E2F1 interaction results in repression of E2F1-mediated transcriptional activity. Finally, overexpression of C/EBPepsilon in human myeloid cells leads to down-regulation of c-Myc. We propose that the interactions between C/EBPepsilon, a tissue-specific transcription factor, and the broad-spectrum proteins, Rb and E2F1, are important in C/EBPepsilon-induced terminal granulocytic differentiation.
Gery
Sigal
S
Cedars-Sinai Medical Center, Davis Bldg 5066, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. gerys@cshs.org
Gombart
Adrian F
AF
Fung
Yuen K
YK
Koeffler
H Phillip
HP
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016259:Genes, myc; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011994:Recombinant Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; C489468:Cebpe protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C070790:CEBPE protein, human