Busturia A, Bienz M
Zoological Institute, University of Zürich, Switzerland.
EMBO J. 1993 Apr;12(4):1415-25. doi: 10.1002/j.1460-2075.1993.tb05785.x.
Homeotic genes determine the developmental fates of cells. Restriction of their expression along the body axis is of prime importance for normal development. We searched for cis-regulatory sequences within Abdominal-B (Abd-B), a homeotic Drosophila gene, by testing genomic Abd-B fragments for their ability to confer beta-galactosidase (beta-gal) expression in transformed embryos. One of the Abd-B fragments, called IAB5, mediates a beta-gal pattern restricted along the body axis to the Abd-B expression domain. Alterations of the IAB5 pattern in gap mutants provide evidence that the protein products of the gap genes hunchback, Krüppel and knirps act as repressors through IAB5. The anterior Abd-B expression limit is apparently determined by Krüppel repression, whereas the knirps repressor may be responsible for the graded Abd-B expression within the Abd-B domain. IAB5 and two other fragments called MCP and FAB show region-specific silencing activity: they suppress at a distance beta-gal expression mediated by a linked heterologous enhancer. Silencing requires hunchback as well as Polycomb function and evidently provides maintenance of Abd-B expression limits throughout embryogenesis. We conclude that transcriptional repression is a key mechanism operating at multiple levels to control Abd-B expression. The striking similarities between the control of Abd-B and of Ultrabithorax, another homeotic Drosophila gene, may point to a universal principle underlying homeotic gene regulation.
同源异型基因决定细胞的发育命运。其沿身体轴的表达限制对于正常发育至关重要。我们通过测试基因组Abd-B片段在转化胚胎中赋予β-半乳糖苷酶(β-gal)表达的能力,来寻找果蝇同源异型基因Abdominal-B(Abd-B)内的顺式调控序列。Abd-B片段之一,称为IAB5,介导一种沿身体轴限制在Abd-B表达域的β-gal模式。间隙突变体中IAB5模式的改变提供了证据,表明间隙基因驼背、Krüppel和knirps的蛋白质产物通过IAB5起阻遏作用。Abd-B的前部表达界限显然由Krüppel的抑制作用决定,而knirps阻遏物可能负责Abd-B域内Abd-B的分级表达。IAB5和另外两个称为MCP和FAB的片段表现出区域特异性沉默活性:它们在远距离抑制由相连的异源增强子介导的β-gal表达。沉默需要驼背以及多梳蛋白功能,并且显然在整个胚胎发育过程中维持Abd-B的表达界限。我们得出结论,转录抑制是在多个水平上控制Abd-B表达的关键机制。Abd-B和另一个果蝇同源异型基因超双胸的控制之间的显著相似性,可能指向同源异型基因调控的一个普遍原则。