Searching across hundreds of databases
The Hedgehog (Hh) signaling pathway directs a multitude of cellular responses during embryogenesis and adult tissue homeostasis. Stimulation of the pathway results in activation of Hh target genes by the transcription factor Ci/Gli, which binds to specific motifs in genomic enhancers. In Drosophila, only a few enhancers (patched, decapentaplegic, wingless, stripe, knot, hairy, orthodenticle) have been shown by in vivo functional assays to depend on direct Ci/Gli regulation. All but one (orthodenticle) contain more than one Ci/Gli site, prompting us to directly test whether homotypic clustering of Ci/Gli binding sites is sufficient to define a Hh-regulated enhancer. We therefore developed a computational algorithm to identify Ci/Gli clusters that are enriched over random expectation, within a given region of the genome. Candidate genomic regions containing Ci/Gli clusters were functionally tested in chicken neural tube electroporation assays and in transgenic flies. Of the 22 Ci/Gli clusters tested, seven novel enhancers (and the previously known patched enhancer) were identified as Hh-responsive and Ci/Gli-dependent in one or both of these assays, including: Cuticular protein 100A (Cpr100A); invected (inv), which encodes an engrailed-related transcription factor expressed at the anterior/posterior wing disc boundary; roadkill (rdx), the fly homolog of vertebrate Spop; the segment polarity gene gooseberry (gsb); and two previously untested regions of the Hh receptor-encoding patched (ptc) gene. We conclude that homotypic Ci/Gli clustering is not sufficient information to ensure Hh-responsiveness; however, it can provide a clue for enhancer recognition within putative Hedgehog target gene loci.
Pubmed ID: 26710299 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Genomatix is a privately held company that offers software, databases, and services aimed at understanding gene regulation at the molecular level representing a central part of systems biology. Its multilayer integrative approach is a working implementation of systems biology principles. Genomatix combines sequence analysis, functional promoter analysis, proprietary genome annotation, promoter sequence databases, comparative genomics, scientific literature data mining, pathway databases, biological network databases, pathway analysis, network analysis, and expression profiling into working solutions and pipelines. It also enables better understanding of biological mechanisms under different conditions and stimuli in the biological context of your data. Some of Genomatix'' most valuable assets are the strong scientific background and the years of experience in research & discovery as well as in development & application of scientific software. Their firsthand knowledge of all the complexities involved in the in-silico analysis of biological data makes them a first-rate partner for all scientific projects involving the evaluation of gene regulatory mechanisms. The Genomatix team has more than a decade of scientific expertise in the successful application of computer aided analysis of gene regulatory networks, which is reflected by more than 150 peer reviewed scientific publications from Genomatix'' scientists More than 35,000 researchers in industry and academia around the world use this technology. The software available in Genomatix are: - GenomatixSuite: GenomatixSuite is our comprehensive software bundle including ElDorado, Gene2Promoter, GEMS Launcher, MatInspector and MatBase. GenomatixSuite PE also includes BiblioSphere Pathway Edition. Chromatin IP Software - RegionMiner: Fast, extensive analysis of genomic regions. - ChipInspector: Discover the real power of your microarray data. Genome Annotation Software - ElDorado: Extended Genome Annotation. - Gene2Promoter: Retrieve & analyze promoters - GPD: The Genomatix Promoter Database, which is now included with Gene2Promoter. Knowledge Mining Software - BiblioSpere : The next level of pathway/genomics analysis. - LitInspector: Literature and pathway analysis for free. Sequence Analysis Software - GEMS Launcher: Our integrated collection of sequence analysis tools. - MalInspector: Search transcription factor binding sites - MatBase: The transcription factor knowledge base. Other (no registration required) Software - DiAlign: Multiple alignment of DNA/protein sequence. - Genomatix tools: Various small tools for sequence statistics, extraction, formatting, etc.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
