The DNA-binding homeo domain of the Oct-2 protein.
The DNA-binding homeo domain of the Oct-2 protein.
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DOI：
10.1101/gad.3.6.739
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发表时间：
1989-06
影响因子：
10.5
通讯作者：
M. Garcia-Blanco;R. G. Clerc;P. Sharp
中科院分区：
文献类型：
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作者：
M. Garcia-Blanco;R. G. Clerc;P. Sharp
普遍存在的核因子Oct-1（也称为OTF-1、NF-A1、NFIII或OBP100）和淋巴细胞特异性细胞蛋白Oct-2（也称为OTF-2或NF-A2）与调节八分子DNA元件ATGCAAAT的特异性相互作用已被广泛表征（Landolfi等人1986；Singh等人1986；Sive和Roeder 1986； Staudt等人1986；Bohmann等人1987；Eaton和Calame 1987； Fletcher等人1987；Scheidereit等人1987；Sturm等人1987）。八聚体元件存在于大量由RNA聚合酶II或RNA聚合酶III服务的启动子和增强子中（Falkner and Zachau 1984; Parslow et al. 1984；相关综述见Folk 1988 and Sollner-Webb 1988），通过对免疫球蛋白启动子的缺失分析，八聚体元件已被证明是一种功能性转录调控元件（Bergman et al. 1984; Mason et al. 1985）。诱变实验表明，octamer元件负责免疫球蛋白启动子的淋巴特异性激活（Wirth等人，1987），并且Oct-2的b淋巴细胞特异性表达暗示它是这些基因的细胞型特异性反式激活因子（Landolfi等人，1986；Staudt等人，1986；Gerster等人，1987；Scheidereit等人，1987；LeBowitz等人，1988）。最近，我们（Clerc等人1988；Staudt等人1988）和其他人（M.M. M611er等人1988；Scheidereit等人1988）分离出编码Oct-2的cdna，并通过Northern分析证明编码克隆蛋白的mrna仅限于淋巴细胞（Clerc等人1988；M.M. mijler等人1988；Staudt等人1988）。此外，在非b淋巴细胞中表达Oct-2 cDNA可激活含有octamer基序的启动子（M.M. Mtiller et al. 1988；回顾请参见Schreiber et al. 1989）。最后，对Oct-2预测氨基酸序列的分析揭示了一系列保守序列：同源结构域（Gehring 1987）、POU盒（Herr et al. 1988）、亮氨酸重复序列（Landschultz et al. 1988）和几个富含酸性氨基酸或谷氨酰胺的区域（Courey and Tjian 1988; Hope et al. 1988; Ptashne 1988）。研究表明，参与DNA与八聚体DNA元件结合的蛋白质区域包括一个60个氨基酸的片段，该片段与Antennapedia同源结构域同源性为31% （Schneuwly et al. 1986; Clerc et al. 1988; Ko et al. 1988）。同源结构域被认为含有与细菌抑制蛋白相似的l - ix结构（Laughon和Scott 1984）。我们将在这里讨论这种结构同源性可以扩展到原核抑制物的三螺旋dna结合域。这一论点是基于同源结构域和几种细菌阻遏物之间的保守氨基酸序列的比较，以及阻遏物-算子共晶的原子结构。这意味着整个同型结构域是dna结合结构域。
The specific interactions of a ubiquitous nuclear factor Oct-1 (also called OTF-1, NF-A1, NFIII, or OBP100) and of a lymphocyte-specific cellular protein Oct-2 (also called OTF-2 or NF-A2) with the regulatory octamer DNA element ATGCAAAT have been characterized extensively (Landolfi et al. 1986; Singh et al. 1986; Sive and Roeder 1986; Staudt et al. 1986; Bohmann et al. 1987; Eaton and Calame 1987; Fletcher et al. 1987; Scheidereit et al. 1987; Sturm et al. 1987). The octamer element is found in a large number of promoters and enhancers that are served by either RNA polymerase II or RNA polymerase III (Falkner and Zachau 1984; Parslow et al. 1984; for reviews, see Folk 1988 and Sollner-Webb 1988), and it has been shown to be a functional transcription regulatory element by deletion analysis of immunoglobulin promoters (Bergman et al. 1984; Mason et al. 1985). Mutagenesis experiments have demonstrated that the octamer element is responsible for the lymphoid-specific activation of immunoglobulin promoters (Wirth et al. 1987), and the B-lymphocyte-specific expression of Oct-2 has implicated it as a cell-type,specific trans-activator of these genes (Landolfi et al. 1986; Staudt et al. 1986; Gerster et al. 1987; Scheidereit et al. 1987; LeBowitz et al. 1988). Recently, we (Clerc et al. 1988; Staudt et al. 1988) and others (M.M. M611er et al. 1988; Scheidereit et al. 1988) have isolated cDNAs that encode Oct-2, and have demonstrated by Northern analysis that mRNAs encoding the cloned protein are restricted to cells of lymphoid origin (Clerc et al. 1988; M.M. MiJller et al. 1988; Staudt et al. 1988). Furthermore, expression of the Oct-2 cDNA in non-B lymphocytes activates promoters containing the octamer motif (M.M. Mtiller et al. 1988; for review, see Schreiber et al. 1989). Finally, analysis of the Oct-2 predicted amino acid sequence has revealed a series of conserved sequences: a homeo domain (Gehring 1987), a POU box (Herr et al. 1988), a leucine repeat (Landschultz et al. 1988), and several regions rich in either acidic amino acids or glutamines (Courey and Tjian 1988; Hope et al. 1988; Ptashne 1988). The region of the protein that is involved in DNA binding to the octamer DNA element has been shown to include a 60-amino-acid segment that is 31% homologous to the Antennapedia homeo domain (Schneuwly et al. 1986; Clerc et al. 1988; Ko et al. 1988). The homeo domain is thought to contain a he l ix tu rn-he l ix structure similar to that of bacterial repressor proteins (Laughon and Scott 1984). We will argue here that this structural homology can be extended to the tri-a-helical DNA-binding domain of prokaryotic repressors. This argument is based on the comparison of conserved amino acid sequences among homeo domains and several bacterial repressors, and on the atomic structure of repressor-operator co-crystals. The implication is that the entire homeo domain is the DNA-binding domain.