title: Dual functions of histone-lysine N-methyltransferase Setdb1 protein at promyelocytic leukemia-nuclear body (PML-NB): maintaining PML-NB structure and regulating the expression of its associated genes.
abstract: Setdb1/Eset is a histone H3 lysine 9 (H3K9)-specific methyltransferase that associates with various transcription factors to regulate gene expression via chromatin remodeling. Here, we report that Setdb1 associates with promyelocytic leukemia (Pml) protein from the early stage of mouse development and is a constitutive member of promyelocytic leukemia (PML)-nuclear bodies (PML-NBs) that have been linked to many cellular processes such as apoptosis, DNA damage responses, and transcriptional regulation. Arsenic treatment, which induces Pml degradation, caused Setdb1 signals to disappear. Setdb1 knockdown resulted in dismantlement of PML-NBs. Immunoprecipitation results demonstrated physical interactions between Setdb1 and Pml. Chromatin immunoprecipitation revealed that, within the frame of PML-NBs, Setdb1 binds the promoter of Id2 and suppresses its expression through installing H3K9 methylation. Our findings suggest that Setdb1 performs dual, but inseparable, functions at PML-NBs to maintain the structural integrity of PML-NBs and to control PML-NB-associated genes transcriptionally.
authors.affiliation: Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, 113 Gwahangno, Yuseong-gu, 305-806 Daejeon, South Korea.
authors.forename: Sunwha
authors.initials: S
authors.lastname: Cho
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D010064:Embryo Implantation; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D051797:Inhibitor of Differentiation Protein 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D011247:Pregnancy; D000071156:Promyelocytic Leukemia Protein; D011496:Protein Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse; D001151:Arsenic