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Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12986-91. Epub 2004 Aug 18.

Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation.

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  • 1Department of Genetics, Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.


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.

Copyright 2004 The National Academy of Sciencs of the USA

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