期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:35
页码:12986-12991
DOI:10.1073/pnas.0402875101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:CCAAT enhancer-binding protein {beta} (C/EBP{beta}), a basic-leucine zipper transcription factor, is an important effector of signals in physiologic growth and cancer. The identification of direct C/EBP{beta} 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/EBP{beta}. We identified 25 potential C/EBP{beta} targets, of which 88% of those tested were confirmed as in vivo C/EBP{beta}-binding sites. Six of these genes also displayed differential expression in C/EBP{beta}-/- livers. Computational analysis revealed that bona fide C/EBP{beta} target genes can be distinguished by the presence of binding motifs for specific additional transcription factors in the vicinity of the C/EBP{beta} site. This approach is generally applicable to the discovery of direct, biologically relevant targets of mammalian transcription factors.