Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60
Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60
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DOI：
10.1007/s00412-009-0247-z
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发表时间：
2010-02-01
期刊：
影响因子：
1.6
通讯作者：
Ehrenhofer-Murray, Ann E.
中科院分区：
文献类型：
--
作者：
Schirling, Corinna;Heseding, Christiane;Ehrenhofer-Murray, Ann E.
MYST 组蛋白乙酰转移酶 (HAT) dTip60 是结合 HAT 和染色质重塑活性的多聚蛋白复合物的一部分。在这里，我们试图深入了解 dTip60 的生物学功能。果蝇中普遍存在的 dTip60 强烈敲低是致命的，而翅膀成虫盘的敲低则导致翅膀发育缺陷。 dTip60 定位于早期胚胎的细胞核，并存在于多线染色体上的大量带间中。细胞培养中去除 dTip60 后的全基因组表达分析表明，它调节果蝇中的大量基因，其中高度富集具有染色质相关功能的基因。令人惊讶的是，这些基因的很大一部分在 dTip60 丢失后上调，表明 dTip60 具有抑制功能和激活功能。 dTip60 蛋白直接位于抑制基因子集的启动子区域，表明在基因抑制中具有直接作用。 dTip60 下调的基因表达特征与曲古抑菌素 A 组蛋白脱乙酰酶抑制的基因表达特征的比较揭示了显着的相关性，表明 dTip60 复合物招募含有 HDAC 的复合物来调节果蝇基因组中的基因表达。
The MYST histone acetyltransferase (HAT) dTip60 is part of a multimeric protein complex that unites both HAT and chromatin remodeling activities. Here, we sought to gain insight into the biological functions of dTip60. Strong ubiquitous dTip60 knock-down in flies was lethal, whereas knock-down in the wing imaginal disk led to developmental defects in the wing. dTip60 localized to the nucleus in early embryos and was present in a large number of interbands on polytene chromosomes. Genome-wide expression analysis upon depletion of dTip60 in cell culture showed that it regulated a large number of genes in Drosophila, among which those with chromatin-related functions were highly enriched. Surprisingly, a significant portion of these genes were upregulated upon dTip60 loss, indicating that dTip60 has repressive as well as activating functions. dTip60 protein was directly located at promoter regions of a subset of repressed genes, suggesting a direct role in gene repression. Comparison of the gene expression signature of dTip60 downregulation with that of histone deacetylase inhibition with trichostatin A revealed a significant correlation, suggesting that the dTip60 complex recruits an HDAC-containing complex to regulate gene expression in the Drosophila genome.