FUNCTIONAL SIMILARITY AND PHYSICAL ASSOCIATION BETWEEN GCN5 AND ADA2 - PUTATIVE TRANSCRIPTIONAL ADAPTERS
FUNCTIONAL SIMILARITY AND PHYSICAL ASSOCIATION BETWEEN GCN5 AND ADA2 - PUTATIVE TRANSCRIPTIONAL ADAPTERS
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DOI：
10.1002/j.1460-2075.1994.tb06806.x
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发表时间：
1994-10-17
期刊：
影响因子：
11.4
通讯作者：
GUARENTE, L
中科院分区：
文献类型：
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作者：
MARCUS, GA;SILVERMAN, N;GUARENTE, L
对GAL4-VP16诱导的毒性具有抗性的酵母突变体的选择先前鉴定了两个基因，ADA2和ADA3，其可以作为一些转录激活结构域的衔接子起作用，从而促进激活。在这里，我们通过相同的选择鉴定了两个新基因，其中一个与GCN 5相同。我们发现，gcn5突变体与ana突变体具有相同的特性，包括生长缓慢，温度敏感性和VP16和GCN 4激活结构域的激活减少。双突变体研究表明，ADA 2和GCN 5功能在一个复杂的或途径。此外，我们证明，GCN 5结合ADA 2的双杂交试验在体内和体外免疫共沉淀。这表明ADA 2和GCN 5是介导转录激活的异聚体复合物的一部分。最后，我们证明了GCN 5的布罗莫结构域的功能重要性，该序列存在于其他全局转录因子中，如SWI/SNF复合物和TATA结合蛋白相关因子。该结构域不是GCN 5和ADA 2之间相互作用所必需的，因此可能介导转录因子的更一般活性。
A selection for yeast mutants resistant to GAL4-VP16-induced toxicity previously identified two genes, ADA2 and ADA3, which may function as adaptors for some transcriptional activation domains and thereby facilitate activation. Here we identify two new genes by the same selection, one of which is identical to GCN5. We show that gcn5 mutants share properties with ana mutants, including slow growth, temperature sensitivity and reduced activation by the VP16 and GCN4 activation domains. Double mutant studies suggest that ADA2 and GCN5 function together in a complex or pathway Moreover, we demonstrate that GCN5 binds to ADA2 both by the two-hybrid assay in vivo and by co-immunoprecipitation in vitro. This suggests that ADA2 and GCN5 are part of a heteromeric complex that mediates transcriptional activation. Finally, we demonstrate the functional importance of the bromodomain of GCN5, a sequence found in other global transcription factors such as the SWI/SNF complex and the TATA binding protein-associated factors. This domain is not required for the interaction between GCN5 and ADA2 and thus may mediate a more general activity of transcription factors.