Promoter-binding and repression of PDGFRB by c-Myc are separable activities

Nucleic Acids Research
Daniel Y L MaoL Z Penn

Abstract

The c-Myc transcription factor represses the mRNA expression of the platelet-derived growth factor receptor beta gene (PDGFRB). Using chromatin immunoprecipitation, we show that c-Myc binds to the proximal promoter of the PDGFRB gene in proliferating rat fibroblasts. Interestingly, mutant c-Myc proteins that are unable to repress PDGFRB gene expression, c-Myc(dBR) and c-Myc(d106-143), are still able to bind to the promoter in vivo. Hence, promoter-binding and repression of PDGFRB by c-Myc are separable activities. We also show that Myc repression of PDGFRB is not dependent on previously described or known transactivator-binding regions, suggesting Myc may be recruited to the promoter by multiple or yet unidentified transcription factors. In the presence of intact promoter-binding by Myc, trichostatin A (TSA) can block Myc repression of PDGFRB in vivo, again demonstrating that promoter-binding and repression are separable. Taken together, we hypothesize that Myc repression of PDGFRB expression occurs by a multi-step mechanism in which repression is initiated after Myc is recruited to the promoter.

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Citations

Nov 26, 2008·Nature Reviews. Cancer·Natalie Meyer, Linda Z Penn
Sep 25, 2004·Nucleic Acids Research·Ran ElkonYosef Shiloh
Aug 25, 2007·Nanomedicine·Hye Hun ParkT Randall Lee
Dec 6, 2011·Biochimica Et Biophysica Acta·Carol ImbrianoRoberto Mantovani
Jun 21, 2011·Journal of Molecular and Cellular Cardiology·Jianhu ZhangAarif Y Khakoo
Aug 15, 2006·Seminars in Cancer Biology·Chi V DangFeng Li
Oct 26, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Romina PonzielliLinda Z Penn
Oct 22, 2013·Biochemical and Biophysical Research Communications·Pin GuoQing Mao
Dec 15, 2005·The Journal of Biological Chemistry·Jagruti H Patel, Steven B McMahon
Nov 4, 2006·The Journal of Biological Chemistry·Jagruti H Patel, Steven B McMahon
Feb 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Murugan KalimuthoKum Kum Khanna
Oct 5, 2017·Scientific Reports·Simone Di GiacomoDaniela Grifoni

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