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Am J Transl Res 2012;4(4):364-375
Review Article
EZH2: a pivotal regulator in controlling cell differentiation
Ya-Huey Chen, Mien-Chie Hung, Long-Yuan Li
Graduate Institute of Cancer Biology, China Medical University, Taichung 40447, Taiwan; Center for Molecular
Medicine, China Medical University Hospital, Taichung 40447, Taiwan; Cancer Biology and Drug Discovery Ph.D.
Program, China Medical University, Taichung 40402, Taiwan; Department of Biotechnology, Asia University,
Taichung 41354, Taiwan; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson
Cancer Center, Houston, Texas 77030, USA
Received September 6, 2012; accepted September 29, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage
differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of
Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has
been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that
not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA
methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin
structures, contributing to tumor progression and the regulation of development and lineage commitment both in
embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing
function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4,
resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent
progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its
targets as well as their roles in stem cell maintenance and cell differentiation. (AJTR1209001).
Keywords: EZH2, polycomb repressive complex, embryonic stem cells, adult stem cells, chromatin modification,
methylation
Address all correspondence to:
Dr. Long-Yuan Li, Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical
University &Hospital, Taichung 40447, Taiwan. Tel: +886 4 22052121; Fax: +886 4 22333496; E-mail:
lyl@mail.cmu.edu.tw; or Dr. Mien-Chie Hung, Department of Molecular and Cellular Oncology, The University of
Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel: 713-792-3668; Fax:
713-794-3270; E-mail: mhung@mdanderson.org
Review Article
EZH2: a pivotal regulator in controlling cell differentiation
Ya-Huey Chen, Mien-Chie Hung, Long-Yuan Li
Graduate Institute of Cancer Biology, China Medical University, Taichung 40447, Taiwan; Center for Molecular
Medicine, China Medical University Hospital, Taichung 40447, Taiwan; Cancer Biology and Drug Discovery Ph.D.
Program, China Medical University, Taichung 40402, Taiwan; Department of Biotechnology, Asia University,
Taichung 41354, Taiwan; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson
Cancer Center, Houston, Texas 77030, USA
Received September 6, 2012; accepted September 29, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage
differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of
Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has
been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that
not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA
methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin
structures, contributing to tumor progression and the regulation of development and lineage commitment both in
embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing
function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4,
resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent
progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its
targets as well as their roles in stem cell maintenance and cell differentiation. (AJTR1209001).
Keywords: EZH2, polycomb repressive complex, embryonic stem cells, adult stem cells, chromatin modification,
methylation
Address all correspondence to:
Dr. Long-Yuan Li, Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical
University &Hospital, Taichung 40447, Taiwan. Tel: +886 4 22052121; Fax: +886 4 22333496; E-mail:
lyl@mail.cmu.edu.tw; or Dr. Mien-Chie Hung, Department of Molecular and Cellular Oncology, The University of
Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel: 713-792-3668; Fax:
713-794-3270; E-mail: mhung@mdanderson.org
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