Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell
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Dong Li1,*, Hui Sun1,3,*, Wen-jing Sun1, Hong-bo Bao4, Shu-han Si1, Jia-lin Fan1, Ping Lin1, Rong-jun Cui1,5, Yu-jia Pan1, Si-min Wen1, Xiu-lan Zheng2,$, Xiao-guang Yu1
1Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
2Department of Ultrasonography, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
3Department of Clinical Laboratory, The Second Clinical Medical School of Inner Mongolia University for The Nationalities, (Inner Mongolia Forestry General Hospital), Hulunbuir, Inner Mongolia 022150, P.R. China
4Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
5Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China
*These authors have contributed equally to this work
Xiao-Guang Yu, email: email@example.com
Keywords: Snail, H3K4me3, RbBP5, EMT, prostate cancer
Received: April 13, 2016 Accepted: August 13, 2016 Published: August 23, 2016
EMT (epithelial- mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/ paracrine manner.
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