Linked Life Data

11566847

Source:http://linkedlifedata.com/resource/pubmed/id/11566847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2001-9-21
pubmed:abstractText
Homothorax (HTH) is a homeobox-containing protein, which plays multiple roles in the development of the embryo and the adult fly. HTH binds to the homeotic cofactor Extradenticle (EXD) and translocates it to the nucleus. Its function within the nucleus is less clear. It was shown, mainly by in vitro studies, that HTH can bind DNA as a part of ternary HTH/EXD/HOX complexes, but little is known about the transcription regulating function of HTH-containing complexes in the context of the developing fly. Here we present genetic evidence, from in vivo studies, for the transcriptional-activating function of HTH. The HTH protein was forced to act as a transcriptional repressor by fusing it to the Engrailed (EN) repression domain, or as a transcriptional activator, by fusing it to the VP16 activation domain, without perturbing its ability to translocate EXD to the nucleus. Expression of the repressing form of HTH in otherwise wild-type imaginal discs phenocopied hth loss of function. Thus, the repressing form was working as an antimorph, suggesting that normally HTH is required to activate the transcription of downstream target genes. This conclusion was further supported by the observation that the activating form of HTH caused typical hth gain-of-function phenotypes and could rescue hth loss-of-function phenotypes. Similar results were obtained with XMeis3, the Xenopus homologue of HTH, extending the known functional similarity between the two proteins. Competition experiments demonstrated that the repressing forms of HTH or XMeis3 worked as true antimorphs competing with the transcriptional activity of the native form of HTH. We also describe the phenotypic consequences of HTH antimorph activity in derivatives of the wing, labial and genital discs. Some of the described phenotypes, for example, a proboscis-to-leg transformation, were not previously associated with alterations in HTH activity. Observing the ability of HTH antimorphs to interfere with different developmental pathways may direct us to new targets of HTH. The HTH antimorph described in this work presents a new means by which the transcriptional activity of the endogenous HTH protein can be blocked in an inducible fashion in any desired cells or tissues without interfering with nuclear localization of EXD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3405-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11566847-Amino Acid Sequence, pubmed-meshheading:11566847-Animals, pubmed-meshheading:11566847-Animals, Genetically Modified, pubmed-meshheading:11566847-Cell Nucleus, pubmed-meshheading:11566847-Conserved Sequence, pubmed-meshheading:11566847-Drosophila Proteins, pubmed-meshheading:11566847-Drosophila melanogaster, pubmed-meshheading:11566847-Evolution, Molecular, pubmed-meshheading:11566847-Extremities, pubmed-meshheading:11566847-Herpes Simplex Virus Protein Vmw65, pubmed-meshheading:11566847-Homeodomain Proteins, pubmed-meshheading:11566847-Phenotype, pubmed-meshheading:11566847-Protein Transport, pubmed-meshheading:11566847-Recombinant Fusion Proteins, pubmed-meshheading:11566847-Repressor Proteins, pubmed-meshheading:11566847-Transcription Factors, pubmed-meshheading:11566847-Transcriptional Activation, pubmed-meshheading:11566847-Xenopus Proteins
pubmed:year
2001
pubmed:articleTitle
Genetic evidence for the transcriptional-activating function of Homothorax during adult fly development.
pubmed:affiliation
Unit of Genetics, Department of Biochemistry, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't