In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element.
Parasegmental (PS)-specific expression of the homeotic genes of the bithorax-complex (BX-C) appears to depend upon the subdivision of the complex into a series of functionally independent cis-regulatory domains. Fab-7 is a regulatory element that lies between iab-6 and iab-7 (the PS11- and PS12-specific cis-regulatory domains, respectively). Deletion of Fab-7 causes ectopic expression of iab-7 in PS11 (where normally only iab-6 is active). Two models have been proposed to account for the dominant Fab-7 phenotype. The first considers that Fab-7 functions as a boundary element that insulates iab-6 and iab-7. The second model envisages that Fab-7 contains a silencer element that keeps iab-7 repressed in parasegments anterior to PS12. Using a P-element inserted in the middle of the Fab-7 region (the bit transposon), we have generated an extensive collection of new Fab-7 mutations that allow us to subdivide Fab-7 into a boundary element and a Polycomb-respond element (PRE). The boundary lies within 1 kb of DNA on the proximal side of the bit transposon (towards iab-6). Deletions removing this element alone cause a complex gain- and loss-of-function phenotype in PS11; in some groups of cells, both iab-6 and iab-7 are active, while in others both iab-6 and iab-7 are inactive. Thus, deletion of the boundary allows activating as well as repressing activities to travel between iab-6 and iab-7. We also provide evidences that the boundary region contains an enhancer blocker element. The Polycomb-response element lies within 0.5 kb of DNA immediately distal to the boundary (towards iab-7). Deletions removing the PRE alone do not typically cause any visible phenotype as homozygotes. Interestingly, weak ectopic activation of iab-7 is observed in hemizygous PRE deletions, suggesting that the mechanisms that keep iab-7 repressed in the absence of this element may depend upon chromosome pairing. These results help to reconcile the previously contradictory models on Fab-7 function and to shed light on how a chromatin domain boundary and a nearby PRE concur in the setting up of the appropriate PS-specific expression of the Abd-B gene of the BX-C.
Mihaly
J
J
Department of Zoology and Animal Biology, University of Geneva, Switzerland.
Hogga
I
I
Gausz
J
J
Gyurkovics
H
H
Karch
F
F
D000005:Abdomen; D000818:Animals; D030801:Animals, Genetically Modified; D002843:Chromatin / Q000502:physiology*; D003433:Crosses, Genetic; D004251:DNA Transposable Elements; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D004742:Enhancer Elements, Genetic; D017353:Gene Deletion; D017344:Genes, Insect; D006720:Homozygote; D019476:Insect Proteins / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D013909:Thorax
D002843:Chromatin; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D019476:Insect Proteins; C066770:Pc protein, Drosophila; D011993:Recombinant Fusion Proteins; D063150:Polycomb Repressive Complex 1