The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription

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Authors: Hee-Bum Kang ; Youngsok Choi ; Jae Myun Lee ; Kyung-Chul Choi ; Han-Cheon Kim ; Jung-Yoon Yoo ; Yoo-Hyun Lee ; Ho-Geun Yoon

MeSH: Active Transport, Cell Nucleus ; Base Sequence ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DNA Primers/genetics ; Enhancer Elements, Genetic ; Histone-Lysine N-Methyltransferase/chemistry ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism* ; Histones/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Ligands ; Male ; Prostate-Specific Antigen/genetics ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/etiology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Protein Interaction Domains and Motifs ; Receptors, Androgen/chemistry ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism* ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Repressor Proteins/chemistry ; Repressor Proteins/genetics ; Repressor Proteins/metabolism* ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Activation

Keywords: Nuclear SET domain-containing 2 ; Androgen receptor ; Histone methyltransferase ; Prostate cancer ; Transcription

Abstract: In this study, we discovered that NSD2 specifically interacts with the DNA-binding domain of androgen receptor (AR) via its HMG domain, and the nuclear translocation of both NSD2 and AR is enhanced in the presence of ligand. Furthermore, we also demonstrated that the over expression of NSD2, but not of NSD2 (DeltaSET) HMT-activity defective mutant, enhanced the mRNA level of PSA in a dose-dependent manner. A chromatin immunoprecipitation assay showed that NSD2 protein is recruited to the enhancer region of the PSA gene by AR in an agonist-enhanced manner. Taken together, these results uncover a potential role for NSD2 in AR-mediated transcription, implicating NSD2 in prostate carcinogenesis.

Full Text: http://www.sciencedirect.com/science/article/pii/S001457930900413X

Appears in Collections:: 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

Yonsei Authors: Kang, Hee Bum(강희범)
Kim, Han Cheon(김한천)
Yoo, Jung Yoon(유정윤) https://orcid.org/0000-0001-9366-3863
Yoon, Ho Geun(윤호근) https://orcid.org/0000-0003-2718-3372
Lee, Yoo Hyun(이유현)
Choi, Kyung Chul(최경철)

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