The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation
The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation
复制标题
DOI：
10.1074/jbc.m008159200
复制
发表时间：
2001-02-02
影响因子：
4.8
通讯作者：
Côté, J
中科院分区：
文献类型：
--
作者：
Eisen, A;Utley, RT;Côté, J
在果蝇中，MSL 复合体是雄性 X 连锁基因的剂量补偿所必需的，并且含有组蛋白乙酰转移酶 MOF。 MOF 乙酰辅酶A 结合位点的点突变会导致男性特异性致死。酵母 Esa1p 是一种 MOF 同源物，对于细胞周期进程至关重要，并且是 NuA4 乙酰转移酶复合物的催化亚基。在这里，我们报告从酵母中纯化的 NuA4，其 Esa1p 的乙酰辅酶A结合域发生点突变，表现出组蛋白乙酰转移酶活性的强烈降低，但对生长没有影响。我们证明，Eaf3p（Esa1p 相关因子 3 蛋白）是一种与果蝇剂量补偿蛋白 MSL3 同源的酵母蛋白，也是 NuA4 复合物的稳定成分。与复合物的其他亚基不同，它不是必需的，并且缺失突变体没有生长表型。从突变菌株中纯化的 NuA4 具有降低的表观分子量，但保留了野生型水平的组蛋白 H4 乙酰转移酶活性。 EAF3缺失和ESA1突变导致PHO5基因表达降低； EAF3 缺失还显着降低了 HIS4 和 TRP4 的表达。这些结果与之前使用 MSL 和 NuA4 复合物获得的结果一起强调了靶向组蛋白 H4 乙酰化对于基因特异性转录激活的重要性。
In Drosophila, the MSL complex is required for the dosage compensation of X-linked genes in males and contains a histone acetyltransferase, MOF. A point mutation in the MOF acetyl-CoA-binding site results in male-specific lethality. Yeast Esa1p, a MOF homolog, is essential for cell cycle progression and is the catalytic subunit of the NuA4 acetyltransferase complex. Here we report that NuA4 purified from yeast with a point mutation in the acetyl-CoA-binding domain of Esa1p exhibits a strong decrease in histone acetyltransferase activity, yet has no effect on growth. We demonstrate that Eaf3p (Esa1p-associated factor-3 protein), a yeast protein homologous to the Drosophila dosage compensation protein MSL3, is also a stable component of the NuA4 complex. Unlike other subunits of the complex, it is not essential, and the deletion mutant has no growth phenotype. NuA4 purified from the mutant strain has a decreased apparent molecular mass, but retains wildtype levels of histone H4 acetyltransferase activity. The EAF3 deletion and the ESA1 mutation lead to a decrease in PHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4 expressions. These results, together with those previously obtained with both the MSL and NuA4 complexes, underscore the importance of targeted histone H4 acetylation for the gene-specific activation of transcription.