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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Oh, Teak-Jung, Adhikari, Abhinav, Mohamad, Trefa, Althobaiti, Aiysha, Davie, Judith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461654/
https://www.ncbi.nlm.nih.gov/pubmed/30979887
http://dx.doi.org/10.1038/s41389-019-0137-z
_version_ 1783410516651147264
author Oh, Teak-Jung
Adhikari, Abhinav
Mohamad, Trefa
Althobaiti, Aiysha
Davie, Judith
author_facet Oh, Teak-Jung
Adhikari, Abhinav
Mohamad, Trefa
Althobaiti, Aiysha
Davie, Judith
author_sort Oh, Teak-Jung
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6461654
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64616542019-04-16 TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma Oh, Teak-Jung Adhikari, Abhinav Mohamad, Trefa Althobaiti, Aiysha Davie, Judith Oncogenesis Article 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. Nature Publishing Group UK 2019-04-12 /pmc/articles/PMC6461654/ /pubmed/30979887 http://dx.doi.org/10.1038/s41389-019-0137-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Oh, Teak-Jung
Adhikari, Abhinav
Mohamad, Trefa
Althobaiti, Aiysha
Davie, Judith
TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title_full TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title_fullStr TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title_full_unstemmed TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title_short TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma
title_sort tbx3 represses tbx2 under the control of the prc2 complex in skeletal muscle and rhabdomyosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461654/
https://www.ncbi.nlm.nih.gov/pubmed/30979887
http://dx.doi.org/10.1038/s41389-019-0137-z
work_keys_str_mv AT ohteakjung tbx3repressestbx2underthecontroloftheprc2complexinskeletalmuscleandrhabdomyosarcoma
AT adhikariabhinav tbx3repressestbx2underthecontroloftheprc2complexinskeletalmuscleandrhabdomyosarcoma
AT mohamadtrefa tbx3repressestbx2underthecontroloftheprc2complexinskeletalmuscleandrhabdomyosarcoma
AT althobaitiaiysha tbx3repressestbx2underthecontroloftheprc2complexinskeletalmuscleandrhabdomyosarcoma
AT daviejudith tbx3repressestbx2underthecontroloftheprc2complexinskeletalmuscleandrhabdomyosarcoma

Ejemplares similares