The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription.
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.
Kang
Hee-Bum
HB
Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea.
Choi
Youngsok
Y
Lee
Jae Myun
JM
Choi
Kyung-Chul
KC
Kim
Han-Cheon
HC
Yoo
Jung-Yoon
JY
Lee
Yoo-Hyun
YH
Yoon
Ho-Geun
HG
D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
C410798:AR protein, human; D017931:DNA Primers; D006657:Histones; D018398:Homeodomain Proteins; D008024:Ligands; C491178:NKX3-1 protein, human; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human; D017430:Prostate-Specific Antigen