TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma

Teak-Jung Oh; Abhinav Adhikari; Trefa Mohamad; Aiysha Althobaiti; Judith Davie

doi:10.1038/s41389-019-0137-z

TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma

Oncogenesis. 2019 Apr 12;8(4):27. doi: 10.1038/s41389-019-0137-z.

Authors

Teak-Jung Oh¹, Abhinav Adhikari², Trefa Mohamad³, Aiysha Althobaiti², Judith Davie⁴

Affiliations

¹ School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
² Department of Biochemistry and Molecular Biology and Simmons Cancer Institute, Southern Illinois University School of Medicine, Carbondale, IL, 62901, USA.
³ Biology Department, College of Science, Salahaddin University, Erbil, Kurdistan, 44002, Iraq.
⁴ Department of Biochemistry and Molecular Biology and Simmons Cancer Institute, Southern Illinois University School of Medicine, Carbondale, IL, 62901, USA. jdavie@siumed.edu.

Abstract

TBX2 and TBX3 function as repressors and are frequently implicated in oncogenesis. We have shown that TBX2 represses p21, p14/19, and PTEN in rhabdomyosarcoma (RMS) and skeletal muscle but the function and regulation of TBX3 were unclear. We show that TBX3 directly represses TBX2 in RMS and skeletal muscle. TBX3 overexpression impairs cell growth and migration and we show that TBX3 is directly repressed by the polycomb repressive complex 2 (PRC2), which methylates histone H3 lysine 27 (H3K27^me). We found that TBX3 promotes differentiation only in the presence of early growth response factor 1 (EGR1), which is differentially expressed in RMS and is also a target of the PRC2 complex. The potent regulation axis revealed in this work provides novel insight into the effects of the PRC2 complex in normal cells and RMS and further supports the therapeutic value of targeting of PRC2 in RMS.

Abstract

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