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Updated: Aug 23, 2026
Human Liver Spheroids from Peripheral Blood for Liver Disease Studies
Published on: January 27, 2023
Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation
Joshua R Friedman1, Brian Larris, Phillip P Le
1Department of Genetics, Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Abstract:
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.
Insights
Researchers identified direct targets of CCAAT enhancer-binding protein beta (C/EBPbeta) using advanced methods. This approach helps discover crucial transcription factor targets in biological processes and diseases like cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- CCAAT enhancer-binding protein beta (C/EBPbeta) is a key transcription factor in growth and cancer.
- Identifying direct C/EBPbeta targets is challenging due to protein compensation and sequence ambiguity.
Purpose of the Study:
- To identify direct and biologically relevant targets of C/EBPbeta in vivo.
- To develop a robust method for discovering transcription factor targets.
Main Methods:
- Combined expression profiling with high-throughput chromatin immunoprecipitation (ChIP).
- Computational analysis of transcription factor binding motifs near C/EBPbeta sites.
Main Results:
- Identified 25 potential C/EBPbeta targets, with 88% confirmed as in vivo binding sites.
- Six target genes showed differential expression in C/EBPbeta-deficient livers.
- Discovered that bona fide targets have specific co-factor binding motifs.
Conclusions:
- The integrated approach successfully identifies direct and relevant C/EBPbeta targets.
- This methodology is broadly applicable for discovering mammalian transcription factor targets.
