Regulation of CCAAT/enhancer-binding protein (C/EBP) activator proteins by heterodimerization with C/EBPgamma (Ig/EBP).
The CCAAT/enhancer-binding proteins (C/EBPs) are basic leucine zipper transcription factors that play important roles in regulating cell growth and differentiation. C/EBP proteins form leucine zipper-mediated homodimers but are also capable of heterodimerizing with other C/EBPs in vitro. Here we show that C/EBPbeta occurs predominantly as a heterodimer that displays rapid mobility in gel shift assays. Biochemical fractionation and antibody supershift assays demonstrate that the C/EBPbeta heterodimeric partner is C/EBPgamma (Ig/EBP), a C/EBP protein that has been implicated as an inhibitor of other family members. Although most cell types express C/EBPbeta.C/EBPgamma heterodimers, macrophages contain a C/EBPbeta partner that is serologically distinct from C/EBPgamma. We found that C/EBPgamma blocked the ability of C/EBPbeta and C/EBPgamma to activate a reporter gene in L cell fibroblasts but did not inhibit a chimeric C/EBPbeta protein containing the GCN4 leucine zipper. Repression by C/EBPgamma occurs at the level of transactivation and requires heterodimerization with the C/EBP partner. C/EBPgamma was an ineffective repressor in HepG2 hepatoma cells despite forming C/EBP heterodimers, and C/EBPalpha was not effectively inhibited in either L or HepG2 cells. Our findings demonstrate that C/EBPgamma modulates C/EBP activity in a cell- and isoform-specific manner.
Parkin
Sara E
SE
Eukaryotic Transcriptional Regulation Section, Regulation of Cell Growth Laboratory, Frederick, Maryland 21702-1201, USA.
Baer
Mark
M
Copeland
Terry D
TD
Schwartz
Richard C
RC
Johnson
Peter F
PF
D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; C497252:CEBPD protein, human; C497253:Cebpd protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D004247:DNA