Kozu Shintaro, Tajiri Reiko, Tsuji Takuya, Michiue Tatsuo, Saigo Kaoru, Kojima Tetsuya
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Dev Biol. 2006 Jun 15;294(2):497-508. doi: 10.1016/j.ydbio.2006.03.015. Epub 2006 Apr 24.
The spatial and temporal regulation of genes encoding transcription factors is essential for the proper development of multicellular organisms. In Drosophila leg development, the distal-most tarsus (ta5) is specified by the strong expression of a pair of Bar homeobox genes in late third instar. This expression is regulated under the control of the ta5 enhancer activated by Bar. No activation of the ta5 enhancer, however, occurs in early third instar when considerable Bar is produced. The ta5 enhancer was comprised of a basal enhancer required for driving Bar expression and a negative regulatory motif serving as a binding site for the heterodimer of Spineless and Tango, homologs of the mammalian dioxin receptor and aryl hydrocarbon nuclear translocator, respectively. The spineless and tango were essential for suppressing the basal enhancer activation in early third instar. The spineless was transiently expressed in early third instar in the Bar expression domain. ta5 Bar expression may thus be temporally regulated through transient inhibition of premature activation of the basal enhancer via specific binding of the Spineless/Tango heterodimer to the negative regulatory motif in early third instar and subsequent release from the inhibition due to the disappearance of spineless expression at later stages.
编码转录因子的基因的时空调控对于多细胞生物的正常发育至关重要。在果蝇腿部发育过程中，最远端的跗节（ta5）是由一对Bar同源框基因在三龄幼虫后期的强烈表达所决定的。这种表达受Bar激活的ta5增强子的调控。然而，在三龄幼虫早期，当产生大量Bar时，ta5增强子并未激活。ta5增强子由驱动Bar表达所需的基础增强子和作为无脊椎动物和探戈异二聚体结合位点的负调控基序组成，无脊椎动物和探戈分别是哺乳动物二噁英受体和芳烃核转运体的同源物。无脊椎动物和探戈对于在三龄幼虫早期抑制基础增强子的激活至关重要。无脊椎动物在三龄幼虫早期在Bar表达域中短暂表达。因此，ta5 Bar表达可能通过在三龄幼虫早期无脊椎动物/探戈异二聚体与负调控基序的特异性结合对基础增强子过早激活的短暂抑制以及后期无脊椎动物表达消失导致的抑制解除来进行时间调控。
