Oncotarget

Research Papers:

A novel role of metal response element binding transcription factor 2 at the Hox gene cluster in the regulation of H3K27me3 by polycomb repressive complex 2

Abdul Aziz Khan, Seok-Jin Ham, Le Ngoc Yen, Haeng Lim Lee, Jounghyun Huh, Hyeongrin Jeon, Myoung Hee Kim and Tae-Young Roh _

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Oncotarget. 2018; 9:26572-26585. https://doi.org/10.18632/oncotarget.25505

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Abstract

Abdul Aziz Khan1, Seok-Jin Ham2, Le Ngoc Yen1, Haeng Lim Lee2, Jounghyun Huh2, Hyeongrin Jeon2, Myoung Hee Kim3 and Tae-Young Roh1,2

1Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk 37673, Republic of Korea

2Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk 37673, Republic of Korea

3Department of Anatomy, Embryology Laboratory, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

Correspondence to:

Tae-Young Roh, email: tyroh@postech.edu

Keywords: PRC2; MTF2; Hox genes; epigenetic silencing; differentiation

Received: March 07, 2018     Accepted: May 07, 2018     Published: May 29, 2018

ABSTRACT

Polycomb repressive complex 2 (PRC2) is known to play an important role in the regulation of early embryonic development, differentiation, and cellular proliferation by introducing methyl groups onto lysine 27 of histone H3 (H3K27me3). PRC2 is tightly associated with silencing of Hox gene clusters and their sequential activation, leading to normal development and differentiation. To investigate epigenetic changes induced by PRC2 during differentiation, deposition of PRC2 components and levels of H3K27me3 were extensively examined using mouse F9 cells as a model system. Contrary to positive correlation between PRC2 deposition and H3K27me3 level, down-regulation of PRC2 components by shRNA and inhibition of EZH1/2 resulted in unexpected elevation of H3K27me3 level at the Hox gene cluster despite its global decrease. We found that metal response element binding transcriptional factor 2 (MTF2), one of sub-stoichiometric components of PRC2, was stably bound to Hox genes. Its binding capability was dependent on other core PRC2 components. A high level of H3K27me3 at Hox genes in Suz12-knock out cells was reversed by knockdown of Mtf2.This shows that MTF2 is necessary to consolidate PRC2-mediated histone methylation. Taken together, our results indicate that expression of Hox gene clusters during differentiation is strictly modulated by the activity of PRC2 secured by MTF2.


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