Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells

doi:10.1016/j.biocel.2018.01.006

. 2018 Mar:96:29-39.

doi: 10.1016/j.biocel.2018.01.006. Epub 2018 Jan 11.

Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells

Lingling Liu¹, Qing Luo², Jinghui Sun³, Yang Ju⁴, Yasuyuki Morita⁵, Guanbin Song⁶

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, People's Republic of China. Electronic address: liulingling2012@163.com.
² Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China. Electronic address: qing.luo@cqu.edu.cn.
³ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, People's Republic of China. Electronic address: sunjhemail@163.com.
⁴ Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: ju@mech.nagoya-u.ac.jp.
⁵ Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: morita@mech.nagoya-u.ac.jp.
⁶ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China. Electronic address: song@cqu.edu.cn.

PMID: 29337251
DOI: 10.1016/j.biocel.2018.01.006

Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells

Lingling Liu et al. Int J Biochem Cell Biol. 2018 Mar.

. 2018 Mar:96:29-39.

doi: 10.1016/j.biocel.2018.01.006. Epub 2018 Jan 11.

Authors

Lingling Liu¹, Qing Luo², Jinghui Sun³, Yang Ju⁴, Yasuyuki Morita⁵, Guanbin Song⁶

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, People's Republic of China. Electronic address: liulingling2012@163.com.
² Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China. Electronic address: qing.luo@cqu.edu.cn.
³ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, People's Republic of China. Electronic address: sunjhemail@163.com.
⁴ Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: ju@mech.nagoya-u.ac.jp.
⁵ Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: morita@mech.nagoya-u.ac.jp.
⁶ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China. Electronic address: song@cqu.edu.cn.

PMID: 29337251
DOI: 10.1016/j.biocel.2018.01.006

Abstract

Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration.

Keywords: Bone marrow-derived mesenchymal stem cells (BMSCs); Chromatin; ERK1/2 signalling; Migration; Nuclear mechanics; Osteopontin.

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Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells

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Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells

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