Activation of transcription through histone H4 acetylation by MOF, an acetyltransferase essential for dosage compensation in Drosophila.
Dosage compensation in Drosophila involves a 2-fold increase in transcription from the single male X relative to the two female X chromosomes. Regulation at the level of the chromosome involves alterations in chromatin organization: male X chromosomes appear decondensed and are marked by acetylation of histone H4 at lysine 16. We demonstrate that MOF, a protein required for dosage compensation with significant sequence similarity to the MYST family of acetyltransferases, is a histone acetyltransferase that acetylates chromatin specifically at histone H4 lysine 16. This acetylation relieves chromatin-mediated repression of transcription in vitro and in vivo if MOF is targeted to a promoter by fusion to a DNA-binding domain. Acetylation of chromatin by MOF, therefore, appears to be causally involved in transcriptional activation during dosage compensation.
Akhtar
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The Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Becker
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PB
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000235:genetics*; D005260:Female; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008297:Male; D009707:Nucleosomes / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D015533:Transcriptional Activation; D014960:X Chromosome / Q000235:genetics
D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D008239:Lysine