title: Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Dong
authors: D
authors: Li
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.|Department 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.
authors: Hui
authors: H
authors: Sun
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Wen-Jing
authors: WJ
authors: Sun
authors: Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
authors: Hong-Bo
authors: HB
authors: Bao
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Shu-Han
authors: SH
authors: Si
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Jia-Lin
authors: JL
authors: Fan
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Ping
authors: P
authors: Lin
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.|Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China.
authors: Rong-Jun
authors: RJ
authors: Cui
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Yu-Jia
authors: YJ
authors: Pan
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Si-Min
authors: SM
authors: Wen
authors: Department of Ultrasonography, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
authors: Xiu-Lan
authors: XL
authors: Zheng
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors: Xiao-Guang
authors: XG
authors: Yu
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D012795:Sialoglycoproteins / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D024363:Transcription Initiation Site; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D010446:Peptide Fragments; C470552:RBBP5 protein, human; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D012795:Sialoglycoproteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; D016212:Transforming Growth Factor beta; C571744:bone sialoprotein (35-62), human
keywords: EMT; H3K4me3; RbBP5; Snail; prostate cancer