An integrated approach for the identification of USF1-centered transcriptional regulatory networks during liver regeneration

•High-throughput evaluation of transcription factor activity changes in early liver regeneration•Construction of transcriptional regulatory networks involving significant gene categories and active transcription factors•Identification of USF1 target genes and USF1-centered regulatory networks during early liver regeneration•Developing a novel strategy for the comprehensive prediction of transcriptional networks in tissues

Liver regeneration after partial hepatectomy (PH) is a synchronized process that is precisely controlled by system-wide transcriptional regulatory networks. To clarify the transcriptional changes and regulatory networks that involve transcription factors (TFs) and their target genes during the priming phase, an advanced mouse oligonucleotide array-based transcription factor assay (MOUSE OATFA), mRNA microarray analysis, bioinformatic analysis and ChIP-on-chip experiments were used. A total of 774 genes were upregulated or downregulated in PH liver samples compared with the sham operation (SH) group. Seventeen TFs showed significant changes in activity in the regenerating livers, some of which have not been extensively studied in previous reports, including upstream stimulatory transcription factor 1 (USF1). The TF signatures from MOUSE OATFA were combined with mRNA expression profiles and ChIP-on-chip analyses to construct experimental transcriptional regulatory networks in regenerating livers. USF1-centered regulatory networks were further confirmed by ChIP assays, revealing some of its target genes and novel coregulatory networks. The combination of MOUSE OATFA with transcriptome profiling and bioinformatic analysis represents a novel paradigm for the comprehensive prediction of transcriptional coregulatory networks during the early phase of liver regeneration.