Topic
Gene interaction
About: Gene interaction is a research topic. Over the lifetime, 3697 publications have been published within this topic receiving 216652 citations.
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17 Oct 2010
TL;DR: In this article, a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls was conducted.
Abstract: To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.
773 citations
TL;DR: It is shown here that the CURLY LEAF gene of Arabidopsis is necessary for stable repression of a floral homeotic gene and encodes a protein with homology to the product of the Polycomb-group gene Enhancer of zeste.
Abstract: Cell fate is determined when the commitment of cells to a particular fate is autonomously maintained, irrespective of their environment. In Drosophila, fate determination is maintained through the action of the Polycomb-group and trithorax-group genes, which are required so that states of homeotic gene activity are inherited through cell division. It is shown here that the CURLY LEAF gene of Arabidopsis is necessary for stable repression of a floral homeotic gene and encodes a protein with homology to the product of the Polycomb-group gene Enhancer of zeste. We suggest that Polycomb-group genes have a similar role in fate determination in plants and animals.
770 citations
TL;DR: It is reported that in the absence of Armadillo, dTcf acts as a transcriptional repressor of Wingless-responsive genes, and it is shown that Groucho act as a corepressor in this process.
Abstract: Wingless/Wnt signalling directs cell-fate choices during embryonic development. Inappropriate reactivation of the pathway causes cancer. In Drosophila, signal transduction from Wingless stabilizes cytosolic Armadillo, which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expression of Wingless-responsive genes. Here we report that in the absence of Armadillo, dTcf acts as a transcriptional repressor of Wingless-responsive genes, and we show that Groucho acts as a corepressor in this process. Reduction of dTcf activity partially suppresses wingless and armadillo mutant phenotypes, leading to derepression of Wingless-responsive genes. Furthermore, overexpression of wild-type dTcf enhances the phenotype of a weak wingless allele. Finally, mutations in the Drosophila groucho gene also suppress wingless and armadillo mutant phenotypes as Groucho physically interacts with dTcf and is required for its full repressor activity.
758 citations
TL;DR: It is shown that Tcf factors physically interact with members of the Groucho family of transcriptional repressors, and secondary-axis formation induced by a dominant-positive Armadillo–Tcf fusion protein was inhibited by Xgrg-4 and enhanced by XGrg-5.
Abstract: Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/β-catenin as a transcriptional co-activator1,2,3,4,5,6,7 However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors6,8,9,10,11,12,13 Here we show that Tcf factors physically interact with members of the Groucho family of transcriptional repressors In transient transfection assays, the Xenopus Groucho homologue XGrg-4 inhibited activation of transcription of synthetic Tcf reporter genes In contrast, the naturally truncated Groucho-family member XGrg-5 enhanced transcriptional activation Injection of XGrg-4 into Xenopus embryos repressed transcription of Siamois and Xnr-3, endogenous targets of β-catenin–Tcf Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos Secondary-axis formation induced by a dominant-positive Armadillo–Tcf fusion protein was inhibited by XGrg-4 and enhanced by XGrg-5 These data indicate that expression of Tcf target genes is regulated by a balance between Armadillo and Groucho
713 citations
TL;DR: A role for the PCP pathway in planar polarization in mammals is demonstrated, and a mutation in Vangl2, a mammalian homologue of the Drosophila PCP gene, is shown to results in significant disruptions in the polarization of stereociliary bundles in mouse cochlea.
Abstract: In mammals, an example of planar cell polarity (PCP) is the uniform orientation of the hair cell stereociliary bundles within the cochlea. The PCP pathway of Drosophila refers to a conserved signalling pathway that regulates the coordinated orientation of cells or structures within the plane of an epithelium. Here we show that a mutation in Vangl2, a mammalian homologue of the Drosophila PCP gene Strabismus/Van Gogh, results in significant disruptions in the polarization of stereociliary bundles in mouse cochlea as a result of defects in the direction of movement and/or anchoring of the kinocilium within each hair cell. Similar, but less severe, defects are observed in animals containing a mutation in the LAP protein family gene Scrb1 (homologous with Drosophila scribble). Polarization defects in animals heterozygous for Vangl2 and Scrb1 are comparable with Vangl2 homozygotes, demonstrating genetic interactions between these genes in the regulation of PCP in mammals. These results demonstrate a role for the PCP pathway in planar polarization in mammals, and identify Scrb1 as a PCP gene.
704 citations