Desplan C, Theis J, O'Farrell P H
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Cell. 1988 Sep 23;54(7):1081-90. doi: 10.1016/0092-8674(88)90123-7.
The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Using deletion constructs expressed as fusion proteins in E. coli, we localized this activity to the conserved homeodomain (HD). The binding site consensus, TCAATTAAAT, is found in clusters in the engrailed regulatory region. Weak binding of the En HD to one copy of a synthetic consensus is enhanced by adjacent copies. The distantly related HD encoded by fushi tarazu binds to the same sites as the En HD, but differs in its preference for related sites. Both HDs bind a second type of sequence, a repeat of TAA. The similarity in sequence specificity of En and Ftz HDs suggests that, within families of DNA binding proteins, close relatives will exhibit similar specificities. Competition among related regulatory proteins might govern which protein occupies a given binding site and consequently determine the ultimate effect of cis-acting regulatory sites.
果蝇发育基因engrailed编码一种序列特异性DNA结合活性。利用在大肠杆菌中表达为融合蛋白的缺失构建体，我们将这种活性定位到保守的同源结构域（HD）。结合位点共有序列TCAATTAAAT在engrailed调控区域成簇存在。Engrailed同源结构域与一个合成共有序列拷贝的弱结合会因相邻拷贝而增强。由ftz编码的远缘相关同源结构域与Engrailed同源结构域结合相同的位点，但在对相关位点的偏好上有所不同。这两种同源结构域都结合第二种序列类型，即TAA重复序列。Engrailed和ftz同源结构域在序列特异性上的相似性表明，在DNA结合蛋白家族中，亲缘关系相近的成员将表现出相似的特异性。相关调控蛋白之间的竞争可能决定哪种蛋白占据给定的结合位点，从而决定顺式作用调控位点的最终效应。
