c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells
The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report t...
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sg-ntu-dr.10356-794732023-02-28T16:58:21Z c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells Lim, Jun Feng Grumont, Raelene Gerondakis, Steve Su, I-hsin Neo, Wen Hao School of Biological Sciences DRNTU::Science::Biological sciences::Biochemistry The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report that c-Rel is a critical activator of Ezh2 transcription in lymphoid cells. In activated primary murine B and T cells, plus human leukemia and multiple myeloma cell lines, recruitment of c-Rel to the first intron of the Ezh2 locus promoted Ezh2 mRNA expression. This up-regulation was abolished in activated c-Rel-deficient lymphocytes and by c-Rel knockdown in Jurkat T cells. Treatment of malignant cells with the c-Rel inhibitor pentoxifylline not only reduced c-Rel nuclear translocation and Ezh2 expression, but also enhanced their sensitivity to the Ezh2-specific drug, GSK126 through increased growth inhibition and cell death. In summary, our demonstration that c-Rel regulates Ezh2 expression in lymphocytes and malignant lymphoid cells reveals a novel transcriptional network in transformed lymphoid cells expressing high levels of Ezh2 that provides a molecular justification for combinatorial drug therapy. Accepted version 2015-02-27T01:22:17Z 2019-12-06T13:26:11Z 2015-02-27T01:22:17Z 2019-12-06T13:26:11Z 2014 2014 Journal Article Neo, W. H., Lim, J. F., Grumont, R., Gerondakis, S., & Su, I.-h. (2014). c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells. Journal of biological chemistry, 289(46), 31693-31707. https://hdl.handle.net/10356/79473 http://hdl.handle.net/10220/25127 10.1074/jbc.M114.574517 25266721 en Journal of biological chemistry © 2014 American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by The Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [Article URL/DOI: http://dx.doi.org/10.1074/jbc.M114.574517]. 26 p. application/pdf |
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DRNTU::Science::Biological sciences::Biochemistry Lim, Jun Feng Grumont, Raelene Gerondakis, Steve Su, I-hsin Neo, Wen Hao c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
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The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report that c-Rel is a critical activator of Ezh2 transcription in lymphoid cells. In activated primary murine B and T cells, plus human leukemia and multiple myeloma cell lines, recruitment of c-Rel to the first intron of the Ezh2 locus promoted Ezh2 mRNA expression. This up-regulation was abolished in activated c-Rel-deficient lymphocytes and by c-Rel knockdown in Jurkat T cells. Treatment of malignant cells with the c-Rel inhibitor pentoxifylline not only reduced c-Rel nuclear translocation and Ezh2 expression, but also enhanced their sensitivity to the Ezh2-specific drug, GSK126 through increased growth inhibition and cell death. In summary, our demonstration that c-Rel regulates Ezh2 expression in lymphocytes and malignant lymphoid cells reveals a novel transcriptional network in transformed lymphoid cells expressing high levels of Ezh2 that provides a molecular justification for combinatorial drug therapy. |
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School of Biological Sciences |
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School of Biological Sciences Lim, Jun Feng Grumont, Raelene Gerondakis, Steve Su, I-hsin Neo, Wen Hao |
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Article |
author |
Lim, Jun Feng Grumont, Raelene Gerondakis, Steve Su, I-hsin Neo, Wen Hao |
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Lim, Jun Feng |
title |
c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
title_short |
c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
title_full |
c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
title_fullStr |
c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
title_full_unstemmed |
c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells |
title_sort |
c-rel regulates ezh2 expression in activated lymphocytes and malignant lymphoid cells |
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2015 |
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https://hdl.handle.net/10356/79473 http://hdl.handle.net/10220/25127 |
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