Genomewide analysis of aryl hydrocarbon receptor binding targets reveals an extensive array of gene clusters that control morphogenetic and developmental programs.
Background: The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus an...
| Publicado en: | Environmental Health Perspectives Vol. 117; no. 7; pp. 1139 - 1147 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Jul2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105396075&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105396075 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Jul2009 vid: 117 iid: 7 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 105396075 2010359290 10.1289/ehp.0800485 NLM19654925 105396075 ppf: 1139 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Genomewide analysis of aryl hydrocarbon receptor binding targets reveals an extensive array of gene clusters that control morphogenetic and developmental programs. aug: au: Sartor MA Schnekenburger M Marlowe JL Reichard JF Wang Y Fan Y Ma C Karyala S Halbleib D Liu X Medvedovic M Puga A affil: Laboratory for Statistical Genomics and Systems Biology, Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA sug: subj: Gene Expression Drug Effects Hydrocarbons Animal Studies Funding Source Mice Reverse Transcriptase Polymerase Chain Reaction ab: Background: The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus and induces transcription of xenobiotic detoxification genes after activation by ligand. Objectives: We conducted an integrative genomewide analysis of AHR gene targets in mouse hepatoma cells and determined whether AHR regulatory functions may take place in the absence of an exogenous ligand. Methods: The network of AHR-binding targets in the mouse genome was mapped through a multipronged approach involving chromatin immunoprecipitation/chip and global gene expression signatures. The findings were integrated into a prior functional knowledge base from Gene Ontology, interaction networks, Kyoto Encyclopedia of Genes and Genomes pathways, sequence motif analysis, and literature molecular concepts. Results: We found the naive receptor in unstimulated cells bound to an extensive array of gene clusters with functions in regulation of gene expression, differentiation, and pattern specification, connecting multiple morphogenetic and developmental programs. Activation by the ligand displaced the receptor from some of these targets toward sites in the promoters of xenobiotic metabolism genes. Conclusions: The vertebrate AHR appears to possess unsuspected regulatory functions that may be potential targets of environmental injury. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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