title: Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1.
abstract: Reversible histone acetylation changes the chromatin structure and can modulate gene transcription. Mammalian histone deacetylase 1 (HDAC1) is a nuclear protein that belongs to a growing family of evolutionarily conserved enzymes catalysing the removal of acetyl residues from core histones and other proteins. Previously, we have identified murine HDAC1 as a growth factor-inducible protein in murine T-cells. Here, we characterise the molecular function of mouse HDAC1 in more detail. Co-immunoprecipitation experiments with epitope-tagged HDAC1 protein reveal the association with endogenous HDAC1 enzyme. We show that HDAC1 can homo-oligomerise and that this interaction is dependent on the N-terminal HDAC association domain of the protein. Furthermore, the same HDAC1 domain is also necessary for in vitro binding of HDAC2 and HDAC3, association with RbAp48 and for catalytic activity of the enzyme. A lysine-rich sequence within the carboxy terminus of HDAC1 is crucial for nuclear localisation of the enzyme. We identify a C-terminal nuclear localisation domain, which is sufficient for the transport of HDAC1 and of reporter fusion proteins into the nucleus. Alternatively, HDAC1 can be shuttled into the nucleus by association with another HDAC1 molecule via its N-terminal HDAC association domain. Our results define two domains, which are essential for the oligomerisation and nuclear localisation of mouse HDAC1.
authors: Institute of Medical Biochemistry, Division of Molecular Biology, Vienna Biocenter, University of Vienna, Austria.
authors: J
authors: J
authors: Taplick
authors: V
authors: V
authors: Kurtev
authors: K
authors: K
authors: Kroboth
authors: M
authors: M
authors: Posch
authors: T
authors: T
authors: Lechner
authors: C
authors: C
authors: Seiser
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4; D016415:Sequence Alignment; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D000939:Epitopes; D006389:Hemagglutinins, Viral; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; C489969:Rbbp4 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; C099683:SIN3A transcription factor; C492042:SIN3B protein, human; C115812:Sin3b protein, mouse; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D008239:Lysine