Polycomb-dependent Ultrabithorax Hox gene silencing induced by high Ultrabithorax levels in Drosophila.
The Ultrabithorax (Ubx) gene of Drosophila specifies the third thoracic and first abdominal segments. Ubx expression is controlled by several mechanisms, including negative regulation by its own product. We show here that if Ubx expression levels are inappropriately elevated, overriding the auto-regulatory control, a permanent repression of Ubx is established. This continuous repression becomes independent of the presence of exogenous Ubx and leads to the paradoxical result that an excess of Ubx results in a phenotype of Ubx loss. The mechanism of permanent repression depends on Polycomb-group genes. Absence of endogenous Ubx transcription when Ubx levels are highly elevated probably activates Polycomb complexes on a Polycomb response element located in the Ubx major intron. This, in turn, brings about permanent repression of Ubx transcription. Similar results are obtained with the gene engrailed, showing that this mechanism of permanent repression may be a general one for genes with negative auto-regulation when levels of expression are transitorily elevated.
Garaulet
Daniel L
DL
Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Foronda
David
D
Calleja
Manuel
M
Sánchez-Herrero
Ernesto
E
D000818:Animals; D030801:Animals, Genetically Modified; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D005810:Multigene Family; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; C066770:Pc protein, Drosophila; D011994:Recombinant Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C512571:trx protein, Drosophila; D063150:Polycomb Repressive Complex 1