Transcription factor Sp3 is regulated by acetylation
Transcription factor Sp3 is regulated by acetylation
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DOI：
10.1093/nar/29.24.4994
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发表时间：
2001-12-15
影响因子：
14.9
通讯作者：
Suske, G
中科院分区：
文献类型：
--
作者：
Braun, H;Koop, R;Suske, G
Sp3是一种与Sp1密切相关的普遍存在的转录因子。先前的分析表明，与Sp1不同，SP3在某些启动子设置下无法激活转录。这是由于在第二个富含谷氨酰胺的激活结构域和DNA结合结构域之间存在一个抑制结构域。为了进一步分析SP3的转录特性，我们从稳定转基因的昆虫细胞中表达并纯化了重组SP3和Sp1作为表位标记蛋白。我们发现，在使用Sp1/Sp3缺失的HeLa核提取物的体外转录实验中，Sp3确实扮演着与Sp1类似的强大激活剂的角色。然而，在同一启动子上，SP3在转染细胞时几乎没有活性。突变研究表明，SP3在体内的低转录活性是由单个赖氨酸残基引起的。我们发现SP3在体内是高度乙酰化的，但不是缺少这种赖氨酸残基的SP3的突变体。我们的结果有力地表明SP3的转录活性受乙酰化的调节。讨论了乙酰化对SP3活性的影响。
Sp3 is a ubiquitous transcription factor closely related to Sp1. Previous analyses showed that, unlike Sp1, Sp3 fails to activate transcription in certain promoter settings. This is due to the presence of an inhibitory domain located between the second glutamine-rich activation domain and the DNA-binding domain. To further analyze the transcriptional properties of Sp3, we have expressed and purified recombinant Sp3 and Sp1 as epitope-tagged proteins from stable transfected insect cells. We found that Sp3 does act as a strong activator similar to Sp1 in an in vitro transcription assay using Sp1/Sp3-depleted HeLa nuclear extract. However, on the same promoter Sp3 is almost inactive when transfected into cells. Mutational studies demonstrate that a single lysine residue is responsible for the low transcriptional activity of Sp3 in vivo. We show that Sp3, but not a mutant of Sp3 that lacks this lysine residue, is highly acetylated in vivo. Our results strongly suggest that the transcriptional activity of Sp3 is regulated by acetylation. The consequences of acetylation for the activity of Sp3 are discussed.