Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation.
CCAAT enhancer-binding protein beta (C/EBPbeta), a basic-leucine zipper transcription factor, is an important effector of signals in physiologic growth and cancer. The identification of direct C/EBPbeta targets in vivo has been limited by functional compensation by other C/EBP family proteins and the low stringency of the consensus sequence. Here we use the combined power of expression profiling and high-throughput chromatin immunoprecipitation to identify direct and biologically relevant targets of C/EBPbeta. We identified 25 potential C/EBPbeta targets, of which 88% of those tested were confirmed as in vivo C/EBPbeta-binding sites. Six of these genes also displayed differential expression in C/EBPbeta-/- livers. Computational analysis revealed that bona fide C/EBPbeta target genes can be distinguished by the presence of binding motifs for specific additional transcription factors in the vicinity of the C/EBPbeta site. This approach is generally applicable to the discovery of direct, biologically relevant targets of mammalian transcription factors.
Department of Genetics, Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Joshua R
JR
Friedman
Brian
B
Larris
Phillip P
PP
Le
T Harshani
TH
Peiris
Athanasios
A
Arsenlis
Jonathan
J
Schug
John W
JW
Tobias
Klaus H
KH
Kaestner
Linda E
LE
Greenbaum
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology; D051379:Mice; D009154:Mutation
D022782:CCAAT-Enhancer-Binding Protein-beta