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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-01-0159.

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Submitted January 17, 2003
Accepted August 21, 2003

C/EBP{epsilon} interacts with Retinoblastoma and E2F1 during granulopoiesis

Sigal Gery*, Adrian F Gombart, Yuen K Fung, and H Phillip Koeffler

Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Division of Hematology/Oncology, Childrens Hospital, Los Angeles, CA, USA

* Corresponding author; email: gerys{at}cshs.org.

CCAAT enhancer binding protein epsilon (C/EBP{epsilon}) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation. Retinoblastoma (Rb) and E2F1 are critical cell-cycle regulators that have also been implicated in several differentiation systems. Here, we demonstrate that C/EBP{epsilon} 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/EBP{epsilon} and Rb enhances C/EBP{epsilon}-mediated transcription of myeloid specific genes both in reporter assays and endogenously. The C/EBP{epsilon}-E2F1 interaction results in repression of E2F1-mediated transcriptional activity. Finally, overexpression of C/EBP{epsilon} in human myeloid cells leads to downregulation of c-Myc. We propose that the interactions between C/EBP{epsilon}, a tissue-specific transcription factor, and the broad-spectrum proteins, Rb and E2F1, are important in C/EBP{epsilon} induced terminal granulocytic differentiation.


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