The class I histone deacetylases of the platyhelminth parasite Schistosoma mansoni.
Histone deacetylases (HDAC) form a conserved enzyme family that control gene expression via the removal of acetyl residues from histones and other proteins and are under increasing investigation as therapeutic targets, notably in cancer and parasitic diseases. To investigate the conservation of these enzymes in the platyhelminth parasite Schistosoma mansoni, we cloned and characterized three class I HDACs, orthologues of mammalian HDAC1, 3 and 8, and confirmed their identities by phylogenetic analysis. The identification of an HDAC8 orthologue showed that it is not vertebrate-specific as previously thought and insertions in its catalytic domain suggest specific enzymatic properties. SmHDAC1, 3, and 8 mRNAs are expressed at all schistosome life-cycle stages. SmHDAC1 repressed transcriptional activity in a mammalian cell line and this activity was dependent on its catalytic activity since transcription was partially restored by treatment with trichostatin A and a catalytic site mutant failed to repress transcription.
Oger
Frédérik
F
Inserm, U 547, Lille, France.
Dubois
Florence
F
Caby
Stéphanie
S
Noël
Christophe
C
Cornette
Jocelyne
J
Bertin
Benjamin
B
Capron
Monique
M
Pierce
Raymond J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic
D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D006877:Hydroxamic Acids; C012589:trichostatin A; D006655:Histone Deacetylases