Disease relevance of Scr

• On the basis of the pattern of chromosomal aberrations that disrupt Scr gene silencing, we propose a model in which two cis-regulatory elements interact to stabilize silencing of any promoter or cis-regulatory element physically between them [1].
• After head involution occurs, Scr protein is also expressed in the ganglion corresponding to parasegment 2 of the ventral nervous system [2].

High impact information on Scr

• In head and thorax the Ubx product overrides Sex combs reduced, Antennapedia, and probably other homeotic genes and dictates its own developmental program [3].
• We characterize a 37-bp element (fkh[250]) derived from the fork head (fkh) gene, a natural target of the Hox gene Sex combs reduced (Scr) [4].
• The lack of proper Antennapedia or Polycomb gene function causes ectopic Scr protein expression [2].
• We find that the Scr gene product is expressed in a dynamic pattern over the course of embryogenesis, beginning in the ectoderm in parasegment 2 while the germ band is elongated and extending to parasegment 3 during the completion of germ band shortening [2].
• The regulatory region of the Scr gene in the Drosophila Antennapedia complex is interrupted by the neighboring ftz transcription unit, yet both genes are specifically activated by their respective enhancers from such juxtaposed positions [5].

Biological context of Scr

• We have identified genes that limit where the homeotic gene Sex combs reduced (Scr) can affect cell fates in the Drosophila embryo [6].
• Third, we analyzed a set of Scr-lacZ enhancer tester constructs [7].
• Taken together, our data suggests that Scr gene expression is differentially regulated both temporally and spatially in a manner that is sensitive to the structure of the locus [8].
• In imaginal cells, some Scr mutations allow cis-regulatory elements on one chromosome to stimulate expression of the promoter on the homolog, a phenomenon that was named transvection by Ed Lewis in 1954 [1].
• Additionally, we have found that the spatial pattern of Scr gene expression in imaginal tissues involved in the development of the adult thorax is governed in part by synapsis of homologous chromosomes in this region of the ANT-C [8].

Anatomical context of Scr

• However, as the salivary gland invaginates, Scr mRNA and protein disappear [9].
• In contrast, Scr regulation in the visceral mesoderm is controlled by an enhancer(s) located in only one DNA fragment [7].
• The homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster is expressed in the labial and prothoracic segments of the ectoderm, in parasegments two and three of the CNS, and in the visceral mesoderm of the anterior and posterior midgut [7].
• In the central nervous system, Scr expression is confined to a narrow band of cells in the subesophageal region of the ventral ganglion [10].
• Here we show in five independent assays the reason for this apparent contradictory requirement of SCR activity in tarsus determination [11].

Associations of Scr with chemical compounds

• The repressor activity of one fragment, normally located in Scr Intron 2, is increased when it is able to homologously pair, a property consistent with genetic data suggesting that Scr exhibits transvection [12].
• Scr encodes a 417-amino-acid DNA-binding protein with sequence similarity to the mouse homologues, HOXA5, B5 and C5 [13].

Physical interactions of Scr

• We find that in the absence of the bithorax complex (BX-C) genes there is Scr expression in the epidermis of the posterior compartments of the thoracic and abdominal parasegments [14].
• In the case of the Drosophila Antennapedia complex, the T1 enhancer bypasses the neighboring ftz gene and interacts with the distant Scr promoter to activate expression in posterior head segments [15].
• A DROSOPHILA: homologue of the regulatory subunit (B'/PR61) of serine-threonine protein phosphatase 2A (dPP2A,B') specifically interacted with the SCR homeodomain [16].

Regulatory relationships of Scr

• In the abdominal cuticle Scr is prevented from inducing prothoracic structures by the three bithorax complex (BX-C) homeotic genes [6].
• Tribolium pb therefore positively regulates distal Scr expression, a role that it has in common with Drosophila pb [17].
• CONCLUSION: These results provide strong evidence that the Scr gene expression is influenced by direct interaction between DSP1 and two Scr regulation elements [18].
• In the epidermis, Antp has been shown to negatively regulate Scr, but it positively regulates Scr in the visceral mesoderm [19].

Other interactions of Scr

• Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes [6].
• We propose the existence of a secondary wave of Scr activation, which takes place during germ band retraction, is triggered by en and requires Antp expression [14].
• The Drosophila proboscis is specified by two Hox genes, proboscipedia and Sex combs reduced, via repression of leg and antennal appendage genes [20].
• Interestingly, while previous studies have concluded that ectopic expression of the homeotic genes Dfd, Scr and Antp has no effect on the segmental identity of the abdominal segments, our results demonstrate that this is not true [21].
• Imaginal discs from these paternally rescued embryos may show discrete patches of expression of Ubx and Scr in inappropriate locations [22].

References