Cloning and analysis of a Toxoplasma gondii histone acetyltransferase: a novel chromatin remodelling factor in Apicomplexan parasites.
The yeast transcriptional adaptor GCN5 functions as a histone acetyltransferase, directly linking chromatin modification to transcriptional regulation. Homologues of yeast GCN5 have been found in Tetrahymena, Drosophila, Arabidopsis and human, suggesting that this pathway of chromatin remodelling is evolutionarily conserved. Consistent with this view, we have identified the Toxoplasma gondii homologue, referred to here as TgGCN5. The gene codes for a protein of 474 amino acids with an estimated molecular mass of 53 kDa. The protein reveals two regions of close similarity with the GCN5 family members, the HAT domain and the bromodomain. Tg GCN5 occurs in a single copy in the T.gondii genome. The introduction of a second copy of TgGCN5 in T.gondii tachyzoites is toxic unless the HAT activity is disrupted by a single point mutation. Full TgGCN5 does not complement the growth defect in a yeast gcn5 (-)mutant strain, but a chimera comprising the T.gondii HAT domain fused to the remainder of yGCN5 does. These data show that T.gondii GNC5 is a histone acetyltransferase attesting to the significance of chromatin remodelling in gene regulation of Apicomplexa.
Hettmann
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Zentrum für Molekulare Biologie Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
Soldati
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D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D019976:Cloning, Organism; D015971:Gene Expression Regulation, Enzymologic; D005816:Genetic Complementation Test; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D015800:Protozoan Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014122:Toxoplasma / Q000201:enzymology* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D002843:Chromatin; D051548:Histone Acetyltransferases; D006657:Histones; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C402103:GCN5 protein, Toxoplasma gondii; D000099224:p300-CBP-Associated Factor