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

Yoshihiro Sato, Yasutake Katoh, Mitsuyo Matsumoto, Masaki Sato, Masayuki Ebina, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi

研究成果: Article

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)8019-8037
ページ数19
ジャーナルJournal of Biological Chemistry
292
19
DOI
出版ステータスPublished - 2017 5 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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