TY - JOUR
T1 - c-Rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells
AU - Wenhao, Neo
AU - Lim, Junfeng
AU - Grumont, Raelene Joy
AU - Gerondakis, Steven Demetrious
AU - I-Hsin, Su
PY - 2014
Y1 - 2014
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Journal of Biological Chemistry
Volume 289, Issue 46, 14 November 2014, Pages 31693-31707
C-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells (Article)
Neo, W.H.a,
Lim, J.F.a,
Grumont, R.b,
Gerondakis, S.b,
Su, I.-H.a
a School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Dr., Singapore, Singapore
b Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
View references (60)
Abstract
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 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.
AB - Check for full text(opens in a new window) Library catalogue(opens in a new window) View at Publisher
Export
Download
More...
Journal of Biological Chemistry
Volume 289, Issue 46, 14 November 2014, Pages 31693-31707
C-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells (Article)
Neo, W.H.a,
Lim, J.F.a,
Grumont, R.b,
Gerondakis, S.b,
Su, I.-H.a
a School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Dr., Singapore, Singapore
b Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
View references (60)
Abstract
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 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.
UR - http://www.jbc.org/content/289/46/31693.full.pdf
U2 - 10.1074/jbc.M114.574517
DO - 10.1074/jbc.M114.574517
M3 - Article
VL - 289
SP - 31693
EP - 31707
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 1083-351X
IS - 46
ER -