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Biochim Biophys Acta. 2014 May;1839(5):415-23. doi: 10.1016/j.bbagrm.2014.03.010. Epub 2014 Mar 28.

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

Author information

1
Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
2
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
3
School of Pharm. Sichuan University, 3-17 Ren-min-nan Road, Chengdu, Sichuan 610041, China.
4
Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: jiaobh@live.cn.
5
Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China; National Engineering Research Center for Beijing Biochip Technology, 18 Life Science Parkway, Beijing 102206, China. Electronic address: ymsun@capitalbio.com.

Abstract

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.

KEYWORDS:

Liver regeneration; Microarray; Transcriptional regulatory network; Upstream stimulatory transcription factor 1

PMID:
24686121
DOI:
10.1016/j.bbagrm.2014.03.010
[Indexed for MEDLINE]
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