mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila

mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila
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DOI:
10.1093/emboj/16.8.2054
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发表时间:
1997-04-15
期刊:
影响因子:
11.4
通讯作者:
Lucchesi, JC
Lucchesi, JC
中科院分区:
生物学1区
文献类型:
--
作者:
Hilfiker, A;HilfikerKleiner, D;Lucchesi, JC

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剂量补偿是确保雄性和雌性具有等量的X染色体基因产物的调节过程。在果蝇中,这是通过相对于雌性,雄性中X连锁基因转录的2倍增强来实现的。转录的增强是由一组调节基因的活性介导的,所述调节基因的特征在于其功能丧失等位基因的雄性特异性致死性,这些基因的产物形成一种复合物,该复合物优先与男性体细胞而非女性体细胞中X染色体上的许多位点相关。剂量补偿复合物的结合与该染色体上特定组蛋白同种型(在Lys 16处乙酰化的组蛋白4)存在的显著增加相关,实验结果和序列分析表明,一个额外的基因,male-absent on the first(mof),编码一个假定的乙酰转移酶,在与剂量补偿相关的特定组蛋白乙酰化中起直接作用,MOF的预测氨基酸序列与几种其它蛋白质,包括人HIV-1达特相互作用蛋白Tip 60,人单核细胞白血病锌指蛋白MOZ和酵母沉默蛋白SAS 3和SAS 2。
Dosage compensation is a regulatory process that insures that males and females have equal amounts of X-chromosome gene products, In Drosophila, this is achieved by a 2-fold enhancement of X-linked gene transcription in males, relative to females, The enhancement of transcription is mediated by the activity of a group of regulatory genes characterized by the male-specific lethality of their loss-of-function alleles, The products of these genes form a complex that is preferentially associated with numerous sites on the X chromosome in somatic cells of males but not of females, Binding of the dosage compensation complex is correlated with a significant increase in the presence of a specific histone isoform, histone 4 acetylated at Lys16, on this chromosome, Experimental results and sequence analysis suggest that an additional gene, males-absent on the first (mof), encodes a putative acetyl transferase that plays a direct role in the specific histone acetylation associated with dosage compensation, The predicted amino acid sequence of MOF exhibits a significant level of similarity to several other proteins, including the human HIV-1 Tat interactive protein Tip60, the human monocytic leukemia zinc finger protein MOZ and the yeast silencing proteins SAS3 and SAS2.