title: Modulation of DNA binding properties of CCAAT/enhancer binding protein epsilon by heterodimer formation and interactions with NFkappaB pathway.
abstract: C/EBP epsilon is a transcription factor involved in myeloid cell differentiation. Along with C/EBP-alpha, -beta, -gamma, -delta, and -zeta, C/EBP-epsilon 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-epsilon preferentially binds DNA as a heterodimer with other C/EBP family members such as C/EBP-delta, CHOP (C/EBP-zeta), and the b-zip family protein ATF4. In this study, we define the consensus binding sites for C/EBP-epsilon dimers and C/EBP-epsilon-ATF4 heterodimers. We show that the activated NFkappaB pathway promotes interaction of the C/EBP-epsilon 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 the activated NFkappaB pathway and C/EBP-epsilon may be important in selective activation of a subset of C/EBP-epsilon-responsive genes.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, University of California at Los Angeles, CA 90048, USA. chumakov@gmail.com
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Chumakov
authors.forename: Agnes
authors.initials: A
authors.lastname: Silla
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Williamson
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C497109:ATF4 protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; C070790:CEBPE protein, human; D051701:Activating Transcription Factor 4