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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 26, 2016; 7(1): 188-205
Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.188
Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.188
Epigenetic alteration to activate Bmp2-Smad signaling in Raf-induced senescence
Mai Fujimoto, Shogo Yamamoto, Hiroyuki Aburatani, Atsushi Kaneda, Genome Science Division, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan
Mai Fujimoto, Yasunobu Mano, Masaki Fukuyo, Atsushi Kaneda, Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Motonobu Anai, Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan
Atsushi Kaneda, CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan
Author contributions: Fujimoto M and Mano Y performed the majority of the experiments; Fujimoto M and Anai M participated in the treatment of animals; Fujimoto M, Mano Y, Yamamoto S and Fukuyo M analyzed the data; Aburatani H and Kaneda A designed and coordinated the research; Fujimoto M, Mano Y and Kaneda A wrote the paper.
Supported by The CREST program, Japan Agency for Medical Research and Development to Kaneda A, and grants from the Uehara Memorial Foundation, Takeda Science Foundation, and Public Trust Surgery Research Fund to Kaneda A.
Institutional review board statement: This study was reviewed and approved by Institutional Review Board of the University of Tokyo.
Institutional animal care and use committee statement: All of the procedures involving animals were reviewed and approved by Institutional Animal Care and Use Committee of the University of Tokyo (IACUC protocol number: RAC120108).
Conflict-of-interest statement: The authors have no conflict of interest.
Data sharing statement: A technical appendix and dataset are available from the corresponding author at kaneda@chiba-u.jp.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Atsushi Kaneda, MD, PhD, Professor, Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan. kaneda@chiba-u.jp
Telephone: +81-43-2262039 Fax: +81-43-2262039
Received: June 26, 2015
Peer-review started: July 16, 2015
First decision: September 17, 2015
Revised: October 30, 2015
Accepted: December 3, 2015
Article in press: December 4, 2015
Published online: February 26, 2016
Processing time: 243 Days and 22.6 Hours
Peer-review started: July 16, 2015
First decision: September 17, 2015
Revised: October 30, 2015
Accepted: December 3, 2015
Article in press: December 4, 2015
Published online: February 26, 2016
Processing time: 243 Days and 22.6 Hours
Core Tip
Core tip: By examining gene expressions and active and repressive histone marks on genome-wide scale, many genes were found to show common expression changes during Ras- and Raf-induced senescence, including genes related to secreted factors and cell cycle. Upregulation of Bmp2 and downregulation of Smad6 were detected and played a role in Raf-induced senescence as well as in Ras-induced senescence. Epigenetic alterations to regulate gene expression were also similar, including gain and loss of active histone mark H3K4me3 and loss of H3K27me3. But epigenetic changes are different in part, e.g., in gain of H3K27me3 in Smad6 promoter region.