The Oct-1 POU domain activates snRNA gene transcription by contacting a region the SNAPc largest subunit that bears sequence similarities to the Oct-1 coactivator OBF-1
The Oct-1 POU domain activates snRNA gene transcription by contacting a region the SNAPc largest subunit that bears sequence similarities to the Oct-1 coactivator OBF-1
复制标题
DOI：
10.1101/gad.12.22.3528
复制
发表时间：
1998-11-15
影响因子：
10.5
通讯作者：
Hernandez, N
中科院分区：
文献类型：
--
作者：
Ford, E;Strubin, M;Hernandez, N
RNA 聚合酶 II 和 III snRNA 基因启动子包含作为增强子一部分的八聚体序列和作为核心启动子一部分的近端序列元件 (PSE)。八聚体和 PSE 分别结合 POU 结构域激活剂 Oct-1 和基础转录因子 SNAP(c)。 Oct-1（但不是 POU 域内具有单个 E7R 突变的 Oct-1）与 SNAP 协同结合，并且实际上将 SNAP 招募到 PSE 上。在这里，我们表明 SNAP 招募是由 Oct-1 POU 结构域和 SNAP 最大亚基 SNAP190 的一小部分区域之间的相互作用介导的。该 SNAP190 区域与 B 细胞特异性 Oct-1 共激活因子 OBF-1 中的一个区域极为相似，OBF-1 是与八聚体结合的 Oct-1 POU 结构域相互作用所必需的。 Oct-1 POU 结构域-SNAP190 相互作用是直接的蛋白质-蛋白质接触，通过分离特异性转换的 SNAP190 突变体来确定，该突变体与 Oct-1 POU E7R 相互作用，但不与野生型 Oct-1 POU 相互作用。我们还表明，这种直接的蛋白质-蛋白质接触导致转录激活。因此，我们在其同源基础转录复合物中鉴定出了人类激活剂 Oct-1 的激活靶点。
The RNA polymerases II and III snRNA gene promoters contain an octamer sequence as part of the enhancer and a proximal sequence element (PSE) as part of the core promoter. The octamer and the PSE bind the POU domain activator Oct-1 and the basal transcription factor SNAP(c), respectively. Oct-1, but not Oct-1 with a single E7R mutation within the POU domain, binds cooperatively with SNAP, and, in effect, recruits SNAP, to the PSE. Here, we show that SNAP, recruitment is mediated by an interaction between the Oct-1 POU domain and a small region of the largest subunit of SNAP, SNAP190. This SNAP190 region is strikingly similar to a region in the B-cell-specific Oct-1 coactivator, OBF-1, that is required for interaction with octamer-bound Oct-1 POU domain. The Oct-1 POU domain-SNAP190 interaction is a direct protein-protein contact as determined by the isolation of a switched specificity SNAP190 mutant that interacts with Oct-1 POU E7R but not with wild-type Oct-1 POU. We also show that this direct protein-protein contact results in activation of transcription. Thus, we have identified an activation target of a human activator, Oct-1, within its cognate basal transcription complex.