title: Regulatory signatures of liver regeneration distilled by integrative analysis of mRNA, histone methylation, and proteomics.
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 confirmedin vitrousing a hepatocarcinoma cell line. The promoter regions of cell-cycle-related genes andFoxm1acquired 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.
authors.affiliation: From the Department of Biochemistry.|Department of Gastroenterological Surgery.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sato
authors.affiliation: From the Department of Biochemistry.|Center for Regulatory Epigenome and Diseases, and.
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Katoh
authors.affiliation: From the Department of Biochemistry.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: From the Department of Biochemistry.|Department of Gastroenterological Surgery.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: From the Department of Biochemistry.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ebina
authors.affiliation: From the Department of Biochemistry.
authors.forename: Ari
authors.initials: A
authors.lastname: Itoh-Nakadai
authors.affiliation: Center for Regulatory Epigenome and Diseases, and.|Department of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Sendai 980-8575, Japan and.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Center for Regulatory Epigenome and Diseases, and.|Department of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Sendai 980-8575, Japan and.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterological Surgery.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: From the Department of Biochemistry, igarashi@med.tohoku.ac.jp.|Center for Regulatory Epigenome and Diseases, and.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Kazuhiko
authors.identifier: 0000-0002-2470-2475
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D000072278:Forkhead Box Protein M1 / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D008115:Liver Regeneration; D008239:Lysine / Q000737:chemistry; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000072278:Forkhead Box Protein M1; C491524:Foxm1 protein, mouse; D006657:Histones; D020543:Proteome; D012333:RNA, Messenger; D008239:Lysine
keywords: functional genomics; histone methylation; proteomics; regeneration; transcriptomics