학술논문

Orthogonal Analysis of C/EBPβ Targets in vivo during Liver Proliferation
Document Type
research-article
Source
Proceedings of the National Academy of Sciences of the United States of America, 2004 Aug . 101(35), 12986-12991.
Subject
Liver
Polymerase chain reaction
Chromosomes
Hepatectomy
Genes
DNA
RNA
Transcription factors
Complementary DNA
Antibodies
Language
English
ISSN
00278424
Abstract
CCAAT enhancer-binding protein β (C/EBPβ), a basic-leucine zipper transcription factor, is an important effector of signals in physiologic growth and cancer. The identification of direct C/EBPβ 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/EBPβ. We identified 25 potential C/EBPβ targets, of which 88% of those tested were confirmed as in vivo C/EBPβ-binding sites. Six of these genes also displayed differential expression in C/ EBPβ -/- livers. Computational analysis revealed that bona fide C/EBPβ target genes can be distinguished by the presence of binding motifs for specific additional transcription factors in the vicinity of the C/EBPβ site. This approach is generally applicable to the discovery of direct, biologically relevant targets of mammalian transcription factors.