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1.
J Mol Biol ; 308(1): 27-38, 2001 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-11302704

RESUMO

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.


Assuntos
Histona Desacetilases/química , Histona Desacetilases/metabolismo , Fatores de Transcrição , Transporte Ativo do Núcleo Celular , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Sequência Conservada/genética , Epitopos/genética , Epitopos/metabolismo , Hemaglutininas Virais/genética , Hemaglutininas Virais/metabolismo , Histona Desacetilase 1 , Histona Desacetilases/genética , Humanos , Lisina/genética , Lisina/metabolismo , Camundongos , Dados de Sequência Molecular , Mutação/genética , Sinais de Localização Nuclear , Proteínas Nucleares/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/metabolismo , Proteína 4 de Ligação ao Retinoblastoma , Alinhamento de Sequência , Complexo Correpressor Histona Desacetilase e Sin3
2.
Mol Cell Biol ; 19(8): 5504-11, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10409740

RESUMO

The members of the Sp1 transcription factor family can act as both negative and positive regulators of gene expression. Here we show that Sp1 can be a target for histone deacetylase 1 (HDAC1)-mediated transcriptional repression. The histone deacetylase inhibitor trichostatin A activates the chromosomally integrated murine thymidine kinase promoter in an Sp1-dependent manner. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex. The interaction between Sp1 and HDAC1 is direct and requires the carboxy-terminal domain of Sp1. Previously we have shown that the C terminus of Sp1 is necessary for the interaction with the transcription factor E2F1 (J. Karlseder, H. Rotheneder, and E. Wintersberger, Mol. Cell. Biol. 16:1659-1667, 1996). Coexpression of E2F1 interferes with HDAC1 binding to Sp1 and abolishes Sp1-mediated transcriptional repression. Our results indicate that one component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1.


Assuntos
Proteínas de Transporte , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Regulação da Expressão Gênica/fisiologia , Histona Desacetilases/fisiologia , Proteínas Repressoras/fisiologia , Fator de Transcrição Sp1/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia , Células 3T3 , Acetilação , Animais , Linhagem Celular , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Genes Reporter , Histona Desacetilase 1 , Histona Desacetilases/genética , Histonas/metabolismo , Humanos , Substâncias Macromoleculares , Camundongos , Modelos Genéticos , Regiões Promotoras Genéticas , Ligação Proteica , Processamento de Proteína Pós-Traducional , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/fisiologia , Proteínas Repressoras/genética , Fase de Repouso do Ciclo Celular , Proteína 1 de Ligação ao Retinoblastoma , Timidina Quinase/genética , Fator de Transcrição DP1 , Ativação Transcricional , Transfecção
3.
FEBS Lett ; 436(3): 349-52, 1998 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-9801146

RESUMO

Proliferation and cell cycle progression of eukaryotic cells are closely linked to changes in chromatin structure and gene expression. By reversible histone acetylation the cell is able to modulate chromatin condensation and accessibility of specific regions within the chromatin. Here, we examined histone H4 acetylation patterns during growth induction of the murine interleukin-2 dependent T cell line B6.1. In order to detect acetylation on each of the four potential target residues we produced a set of antibodies recognizing specifically acetylated lysine 5, 8, 12 and 16 in the N-terminal tail of histone H4. Acetylation was generally low in resting T cells, but increased after stimulation with a specific kinetics for each lysine. Lysine 16 was acetylated during the G1 phase and deacetylated during S phase. H4 acetylation on lysine 5, 8 and 12, in contrast, was induced before cells started to replicate, and persisted until cells entered mitosis. Treatment of resting B6.1 cells with the specific deacetylase inhibitor trichostatin A (TSA) led to H4 hyperacetylation at all four lysine residues indicating that the histone modification can occur in the absence of replication. After release from TSA treatment normal H4 acetylation levels were reestablished by extremely rapid deacetylation of lysines 5, 8, 12 and 16. The deacetylation step was 60-100 times faster than TSA induced acetylation and equally efficient in resting and exponentially growing T cells. Our results indicate the presence of cell cycle regulated lysine specific acetylating and deacetylating activities in mouse T cells.


Assuntos
Histonas/metabolismo , Interleucina-2/farmacologia , Linfócitos T/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Histonas/química , Cinética , Lisina/análogos & derivados , Lisina/análise , Camundongos , Mitose , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos
6.
Asklepii ; 1: 79-[87], 1970.
Artigo em Russo | MEDLINE | ID: mdl-11636555

RESUMO

The military and revolutionary activity of Bulgarian physicians (enlighteners) during the Turkish yoke is closely connected with the wars of Russia waged against Turkey. The Bulgarian physicians were active in the military and revolutionary field also during the Serbian-Turkish war in 1876. About 20 Bulgarian physicians and pharmacologists were included in the composition of the Russian sanitary missions and in those of the Roumanians. The participation in the above wars enabled the Bulgarian physicians to get acquainted as early as before the liberation, with the problems of military medicine--an experience which proved very helpful in the establishment of the first Bulgarian field medical service during the Liberation war.


Assuntos
Cooperação Internacional , Medicina Militar , Política , Guerra , Bulgária , História do Século XIX , Federação Russa , Turquia
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