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.
Friedman
Joshua R
JR
Department of Genetics, Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Larris
Brian
B
Le
Phillip P
PP
Peiris
T Harshani
TH
Arsenlis
Athanasios
A
Schug
Jonathan
J
Tobias
John W
JW
Kaestner
Klaus H
KH
Greenbaum
Linda E
LE
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