Sipos L, Mihály J, Karch F, Schedl P, Gausz J, Gyurkovics H
Hungarian Academy of Sciences, Biological Research Center, Institute of Genetics, H-6701 Szeged, Hungary.
Genetics. 1998 Jun;149(2):1031-50. doi: 10.1093/genetics/149.2.1031.
The Abd-B gene, one of the three homeotic genes in the Drosophila bithorax complex (BX-C), is required for the proper identity of the fifth through the eighth abdominal segments (corresponding to parasegments 10-14) of the fruitfly. The morphological difference between these four segments is due to the differential expression of Abd-B, which is achieved by the action of the parasegment-specific cis-regulatory regions infra-abdominal-5 (iab-5), -6, -7 and -8. The dominant gain-of-function mutation Frontabdominal-7 (Fab-7) removes a boundary separating two of these cis-regulatory regions, iab-6 and iab-7. As a consequence of the Fab-7 deletion, the parasegment 12- (PS12-) specific iab-7 is ectopically activated in PS11. This results in the transformation of the sixth abdominal segment (A6) into the seventh (A7) in Fab-7 flies. Here we report that point mutations of the Abd-B gene in trans suppress the Fab-7 phenotype in a pairing-dependent manner and thus represent a type of transvection. We show that the observed suppression is the result of trans-regulation of the defective Abd-B gene by the ectopically activated iab-7. Unlike previously demonstrated cases of trans-regulation in the Abd-B locus, trans-suppression of Fab-7 is sensitive to heterozygosity for chromosomal rearrangements that disturb homologous pairing at the nearby Ubx locus. However, in contrast to Ubx, the transvection we observed in the Abd-B locus is insensitive to the allelic status of zeste. Analysis of different deletion alleles of Abd-B that enhance trans-regulation suggests that an extensive upstream region, different from the sequences required for transcription initiation, mediates interactions between the iab cis-regulatory regions and the proximal Abd-B promoter. Moreover, we find that the amount of DNA deleted in the upstream region is roughly proportional to the strength of trans-interaction, suggesting that this region consists of numerous discrete elements that cooperate in tethering the iab regulatory domains to Abd-B. Possible implications of the tethering complex for the regulation of Abd-B are discussed. In addition, we present evidence that the tenacity of trans-interactions in the Abd-B gene may vary, depending upon the tissue and stage of development.
Abd - B基因是果蝇双胸复合体（BX - C）中的三个同源异型基因之一，对于果蝇第五至第八腹节（对应于副节10 - 14）的正常特征形成是必需的。这四个腹节之间的形态差异是由于Abd - B的差异表达造成的，而这种差异表达是通过腹节特异性顺式调控区域腹下-5（iab - 5）、-6、-7和-8的作用实现的。显性功能获得性突变前腹部-7（Fab - 7）消除了分隔其中两个顺式调控区域iab - 6和iab - 7的边界。由于Fab - 7缺失，副节12 -（PS12 -）特异性的iab - 7在PS11中被异位激活。这导致Fab - 7果蝇的第六腹节（A6）转化为第七腹节（A7）。在此我们报道，Abd - B基因的反式点突变以配对依赖的方式抑制Fab - 7表型，因此代表一种反式效应。我们表明观察到的抑制是异位激活的iab - 7对有缺陷的Abd - B基因进行反式调控的结果。与先前在Abd - B基因座中证明的反式调控情况不同，Fab - 7的反式抑制对染色体重排的杂合性敏感，这些重排会干扰附近Ubx基因座的同源配对。然而，与Ubx相反，我们在Abd - B基因座中观察到的反式效应对zeste的等位基因状态不敏感。对增强反式调控的Abd - B不同缺失等位基因的分析表明，一个广泛的上游区域，不同于转录起始所需的序列，介导了iab顺式调控区域与近端Abd - B启动子之间的相互作用。此外，我们发现上游区域缺失的DNA量大致与反式相互作用的强度成正比，这表明该区域由许多离散元件组成，它们协同作用将iab调控域与Abd - B相连。讨论了这种连接复合体对Abd - B调控的可能影响。此外，我们提供证据表明，Abd - B基因中反式相互作用的强度可能因组织和发育阶段而异。
