Regulatory signatures of liver regeneration distilled by integrative analysis of mRNA, histone methylation, and proteomics

Yoshihiro Sato, Yasutake Kato, Mitsuyo Matsumoto, Masaki Sato, Masayuki Ebina, Ari Ito, Ryo Funayama, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The capacity of the liver to regenerate is likely to be encoded as a plasticity of molecular networks within the liver. By applying a combination of comprehensive analyses of the epigenome, transcriptome, and proteome, we herein depict the molecular landscape of liver regeneration. We demonstrated that histone H3 Lys-4 was trimethylated at the promoter regions of many loci, among which only a fraction, including cell-cycle-related genes, were transcriptionally up-regulated. A cistrome analysis guided by the histone methylation patterns and the transcriptome identified FOXM1 as the key transcription factor promoting liver regeneration, which was confirmed in vitro using a hepatocarcinoma cell line. The promoter regions of cell-cycle-related genes and Foxm1 acquired higher levels of trimethylated histone H3 Lys-4, suggesting that epigenetic regulations of these key regulatory genes define quiescence and regeneration of the liver cells. A quantitative proteome analysis of the regenerating liver revealed that conditional protein degradation also mediated regeneration-specific protein expression. These sets of informational resources should be useful for further investigations of liver regeneration.

Original languageEnglish
Pages (from-to)8019-8037
Number of pages19
JournalJournal of Biological Chemistry
Volume292
Issue number19
DOIs
Publication statusPublished - 2017 May 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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