title: Nuclear localization signal domain of HDAC3 is necessary and sufficient for the expression regulation of MDR1.
abstract: Histone acetylation/deacetylation has been known to be associated with the transcriptional regulation of various genes. The role of histone deacetylase-3 in the expression regulation of MDR1 was investigated. The expression level of HDAC3 showed an inverse relationship with the expression level of MDR1. Wild-type HDAC3, but not catalytic mutant HDAC3(S424A), negatively regulated the expression of MDR1. Wild-type HDAC3, but not catalytic mutant HDAC3(S424A), showed binding to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the binding of Ac-H3(K9/14) and Ac-H4(K16) around the MDR1 promoter sequences. The nuclear localization signal domain of HDAC3 was necessary, and sufficient for the binding of HDAC3 to the MDR1 promoter sequences and for conferring sensitivity to microtubule-targeting drugs.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000107:Acetylation; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D056945:Hep G2 Cells; D006655:Histone Deacetylases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000099186:Histone Deacetylase 3
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006655:Histone Deacetylases; D006657:Histones; D000099186:Histone Deacetylase 3