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首页> 外文期刊>Journal of Molecular Biology >A conserved central region of yeast Ada2 regulates the histone acetyltransferase activity of Gcn5 and interacts with phospholipids.
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A conserved central region of yeast Ada2 regulates the histone acetyltransferase activity of Gcn5 and interacts with phospholipids.

机译：酵母Ada2的保守中心区域调节Gcn5的组蛋白乙酰转移酶活性并与磷脂相互作用。

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The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex of Saccharomyces cerevisiae contains more than 20 components that acetylate and deubiquitylate nucleosomal histones. Its acetyltransferase, Gcn5, preferentially acetylates histones H3 and H2B and is regulated through interactions with Ada2 and Ngg1/Ada3. Sequence alignments of Ada2 homologs indicate a conserved approximately 120-amino-acid-residue central region. To examine the function of this region, we constructed ada2 alleles with mutations of clustered conserved residues. One of these alleles, ada2-RLR (R211S, L212A, and R215A), resulted in an approximately threefold reduction in transcriptional activation of the PHO5 gene and growth changes that parallel deletion of ada2. Microarray analyses further revealed that ada2-RLR alters expression of a subset of those genes affected by deletion of ada2. Indicative of Ada2-RLR affecting Gcn5 function, Ada2-RLR resulted in a decrease in Gcn5-mediated histone acetylation in vitro to a level approximately 40%that with wild-type Ada2. In addition, in vivo acetylation of K16 of histone H2B was almost totally eliminated at Ada2-regulated promoters in the ada2-RLR strain, while acetylation of K9 and K18 of histone H3 was reduced to approximately 40% of wild-type levels. We also show that the central region of Ada2 interacts with phospholipids. Since phosphatidylserine binding paralleled Ada2 function, we suggest that lipid binding may play a role in the function or regulation of the SAGA complex.
机译：酿酒酵母的SAGA（Spt-Ada-Gcn5乙酰转移酶）复合物包含20多个使核小体组蛋白乙酰化和去泛素化的组分。它的乙酰基转移酶Gcn5优先乙酰化组蛋白H3和H2B，并通过与Ada2和Ngg1 / Ada3的相互作用进行调节。 Ada2同源物的序列比对表明保守的大约120个氨基酸残基的中央区域。为了检查该区域的功能，我们构建了具有簇状保守残基突变的ada2等位基因。这些等位基因之一ada2-RLR（R211S，L212A和R215A）导致PHO5基因的转录激活降低约三倍，并且生长变化与ada2平行缺失。微阵列分析进一步显示，ada2-RLR改变了受ada2缺失影响的那些基因子集的表达。指示Ada2-RLR影响Gcn5功能，Ada2-RLR导致体外Gcn5介导的组蛋白乙酰化水平降低至野生型Ada2的水平约40％。另外，在ada2-RLR菌株中，在Ada2调节的启动子上，组蛋白H2B的K16的体内乙酰化几乎被完全消除，而组蛋白H3的K9和K18的乙酰化被降低至野生型水平的约40％。我们还表明，Ada2的中央区域与磷脂相互作用。由于磷脂酰丝氨酸结合平行Ada2功能，我们建议脂质结合可能在SAGA复合物的功能或调节中发挥作用。

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