Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 35, Pages 12986-12991Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0402875101
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Funding
- NIDDK NIH HHS [DK56947, U01 DK056947, DK056669, R24 DK056947, DK49210, R01 DK056669, P01 DK049210] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008638, 5T32GM008638] Funding Source: Medline
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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.
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