Submitted September 12, 2005
Accepted August 14, 2006
Modulation of DNA binding properties of CCAAT/enhancer
binding protein epsilon by heterodimer formation and
interactions with NFkappaB pathway
Alexey M Chumakov*, Agnes Silla, Elizabeth A Williamson, and H. Phillip Koeffler
Dept of Medicine, Hematology/Oncology, Cedars-Sinai Research Center, and Dept of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA
University of New Mexico Cancer Research Facility, Albuquerque, NM
* Corresponding author; email: chumakov{at}gmail.com.
C/EBP epsilon is a transcription factor involved in myeloid cell differentiation. Along with C/EBP-
, -
, -
, -
and -
, C/EBP-
belongs to the family of CCAAT/enhancer binding proteins that are implicated in control of growth and differentiation of several cell lineages, in inflammation and stress response. We have previously shown that C/EBP- preferentially binds DNA as a heterodimer with other C/EBP family members such as C/EBP-, CHOP (C/EBP-), and the b-zip family protein ATF4. In this study, we define the consensus binding sites for C/EBP- dimers and C/EBP- - ATF4 heterodimers. We show that activated NFkappaB pathway promotes interaction of the C/EBP- subunit with its cognate DNA binding site via interaction with RelA. RelA-C/EBP interaction is enhanced by phosphorylation of threonine at amino acid 75 and results in increased DNA binding compared with the wild-type nonphosphorylated C/EBP both in vitro and in vivo. We suggest that interaction of activated NFkappaB pathway and C/EBP- may be important in selective activation of a subset of C/EBP- - responsive genes.
