Transvection in the Drosophila Ultrabithorax gene: a Cbx1 mutant allele induces ectopic expression of a normal allele in trans.

Abstract

In wild-type Drosophila melanogaster larvae, the Ultrabithorax (Ubx) gene is expressed in the haltere imaginal discs but not in the majority of cells of the wing imaginal discs. Ectopic expression of the Ubx gene in wing discs can be elicited by the presence of Contrabithorax (Cbx) gain-of-function alleles of the Ubx gene or by loss-of-function mutations in Polycomb (Pc) or in other trans-regulatory genes which behave as repressors of Ubx gene activity. Several Ubx loss-of-function alleles cause the absence of detectable Ubx proteins (UBX) or the presence of truncated UBX lacking the homeodomain. We have compared adult wing phenotypes with larval wing disc UBX patterns in genotypes involving double mutant chromosomes carrying in cis one of those Ubx mutations and the Cbx1 mutation. We show that such double mutant genes are (1) active in the same cells in which the single mutant Cbx1 is expressed, although they are unable to yield functional proteins, and (2) able to induce ectopic expression of a normal homologous Ubx allele in a part of the cells in which the single mutant Cbx1 is active. That induction is conditional upon pairing of the homologous chromosomes (the phenomenon known as transvection), and it is not mediated by UBX. Depletion of Pc gene products by Pc3 mutation strongly enhances the induction phenomenon, as shown by (1) the increase of the number of wing disc cells in which induction of the homologous allele is detectable, and (2) the induction of not only a paired normal allele but also an unpaired one.

Homologous association of the Bithorax-Complex during embryogenesis: consequences for transvection in Drosophila melanogaster

“…1C). Both of these transpositions have been shown by Castelli-Gair and coworkers to completely disrupt transvection phenotypes at the Ubx locus (Castelli-Gair et al, 1990;Micol and García-Bellido, 1988). A strong reduction but not complete inhibition of transvection of the abd-A and the Abd-B genes was found for Tp(3;1)P115 (Hopmann et al, 1995;Jijakli and Ghysen, 1992).…”

“…Although the transvection phenotype is defined in larval and adult Drosophila, the spatial pattern of the transcriptional state of the BX-C genes in the embryo predetermines whether or not the genes are transcriptionally competent in the larvae and adult (Fauvarque et al, 1995;Paro, 1993;Pirrotta, 1995;Simon, 1995). The RNA (or macromolecular transport) model (Castelli-Gair et al, 1990;Mathog, 1990;Lewis, 1954) postulates the obligatory production of a short-lived effector that interacts with the promoter. The transvection phenotype is then determined by the proximity of homologous loci during the lifetime of the effector whereby the effector can interact with the promoter in trans.…”

“…The trans-interaction has a probability that is much lower than that for the cis-interaction as has been shown for the yellow locus (Geyer et al, 1990). If we assume that trans-looping is at least an order of magnitude less efficient than cis looping, as can be deduced from the data of Castelli-Gair et al (1990) then a reduction of pairing to 20-30% could lead to a very low probability of a competent transcription complex being assembled. It is assumed that the M. J. Gemkow, P. J. Verveer and D. J. Arndt-Jovin initiation complex would have to be formed anew for each transcript, as is the case at the β-globin locus (Wijgerde et al, 1995).…”

“…The genetic experiments showed that homologous chromosomes can influence each other, phenomena that are collectively called trans-sensing effects [reviewed in Henikoff, 1997]. The most intensively studied effect is transvection, the control of genes by regulatory sequences in trans, first described by Lewis (Lewis, 1954) and investigated in detail for the Bithorax Complex (BX-C) (Babu et al, 1987;Castelli-Gair et al, 1990;Martinez-Laborda et al, 1992;Mathog, 1990;Micol and García-Bellido, 1988). These papers postulate two models of how transvection might occur: (a) direct interaction of the homologous chromosome elements, or (b) transmission of a soluble macromolecule such as a short-lived RNA transcript from one homologue to the other.…”

A micro-evolutionary change in target binding sites as a key determinant of Ultrabithorax function in Drosophila

“…In Drosophila melanogaster, the Hox protein Ultrabithorax (Ubx) specifies the development of halteres in the third thoracic (T3) segment (Lewis, 1978 and many other reports; reviewed in Khan et al 2020). Loss of function mutations of Ubx gives rise to four winged flies with complete duplication of the T2 segment in place of T3 ( Lewis 1978;Bender et al 2007), while overexpression of Ubx in larval wing discs lead to wing to haltere transformations (Cabrera et al 1985;White and Akam 1985;White and Wilcox 1985;Castelli-Gair et al 1990). Ubx is known to bind, in vitro, to motifs with consensus binding site (TTTAATTA) having a TAAT core sequence (hereafter referred to as TAAT motif) (Ekker et al 1991;Noyes et al 2008;Berger et al 2008).…”