Cooperative binding of the yeast Spt10p activator to the histone upstream activating sequences is mediated through an N-terminal dimerization domain.
Cooperative binding of the yeast Spt10p activator to the histone upstream activating sequences is mediated through an N-terminal dimerization domain.
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DOI：
10.1093/nar/gkl1079
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发表时间：
2007
影响因子：
14.9
通讯作者：
Clark DJ
中科院分区：
文献类型：
--
作者：
Mendiratta G;Eriksson PR;Clark DJ
酵母Spt10p激活因子是一种假定的组蛋白乙酰转移酶（HAT），具有序列特异性dna结合域（DBD），与组蛋白基因启动子中的上游激活序列（UAS元件）结合。Spt10p与一对组蛋白UAS元件结合，具有极好的正协同性。讨论了这种协同作用的分子基础。Spt10p（640个残基）是一个细长的二聚体，但分离的DBD（283-396个残基）是一个单体，与DNA不合作结合。由n端结构域（NTD）、HAT结构域和DBD（残基1-396）组成的Spt10p片段是二聚体，而由DBD和c端结构域（残基283-640）组成的重叠Spt10p片段是非合作结合的，是单体。这些观察结果表明，协同结合需要二聚化。分离的NTD（残基1-98）是二聚体，负责二聚化。我们提出，协同性涉及到Spt10p二聚体的构象变化，这有助于同时识别两个UAS元素。在体内，NTD的缺失会导致生长不良，但不会阻止HTA1启动子的结合，这表明二聚化在生物学上是重要的。残基1-396足以满足正常生长，表明Spt10p的关键功能存在于n端结构域。
The yeast Spt10p activator is a putative histone acetyltransferase (HAT) possessing a sequence-specific DNA-binding domain (DBD) which binds to the upstream activation sequences (UAS elements) in the histone gene promoters. Spt10p binds to a pair of histone UAS elements with extreme positive cooperativity. The molecular basis of this cooperativity was addressed. Spt10p (640 residues) is an elongated dimer, but the isolated DBD (residues 283–396) is a monomer and binds non-cooperatively to DNA. A Spt10p fragment comprising the N-terminal domain (NTD), HAT domain and DBD (residues 1–396) binds cooperatively and is a dimer, whereas an overlapping Spt10p fragment comprising the DBD and C-terminal domains (residues 283–640) binds non-cooperatively and is a monomer. These observations imply that cooperative binding requires dimerization. The isolated NTD (residues 1–98) is a dimer and is responsible for dimerization. We propose that cooperativity involves a conformational change in the Spt10p dimer which facilitates the simultaneous recognition of two UAS elements. In vivo, deletion of the NTD results in poor growth, but does not prevent the binding at the HTA1 promoter, suggesting that dimerization is biologically important. Residues 1–396 are sufficient for normal growth, indicating that the critical functions of Spt10p reside in the N-terminal domains.
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