| http://purl.uniprot.org/citations/18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18508077 | http://www.w3.org/2000/01/rdf-schema#comment | "Latent TGFbeta-binding protein 1 (LTBP-1) is a key regulator of TGFbeta targeting and activation in the extracellular matrix. LTBP-1 is recognized as a major docking molecule to localize, and possibly to activate, TGFbeta in the extracellular matrix. Despite this relevant function, the molecular mechanisms regulating Ltbp-1 transcription remain largely unknown. Previous results from our laboratory revealed that mouse embryonic fibroblasts (MEF) lacking dioxin receptor (AhR) had increased Ltbp-1 mRNA expression and elevated TGFbeta activity, suggesting that AhR repressed Ltbp-1 transcription. Here, we have cloned the mouse Ltbp-1 gene promoter and analysed its mechanism of transcriptional repression by AhR. Reporter gene assays, AhR over-expression and site-directed mutagenesis showed that basal Ltbp-1 transcription is AhR-dependent. Chromatin immunoprecipitation (ChIP) and RNA interference (RNAi) revealed that AhR regulates Ltbp-1 transcription by a mechanism involving recruitment of co-activators such as CREB1 and co-repressors such as HDAC2 to the Ltbp-1 promoter. In AhR-expressing (AhR+/+) MEF cells, the recruitment of HDAC1, 2 and 4 correlated with decreased K8H4 acetylation and impaired binding of pCREB(Ser133) to the Ltbp-1 promoter, likely maintaining a constitutive repressed state. AhR-/-MEF cells had the opposite pattern of HDACs and pCREB1(Ser133) binding to Ltbp-1 promoter, and therefore, over-expressed Ltbp-1 mRNA. In agreement, siRNA for HDAC2 increased Ltbp-1 expression and K8H4 acetylation in AhR+/+ but not in AhR-/-MEF cells. We suggest that HDAC2 binding keeps Ltbp-1 promoter repressed in AhR+/+ MEF cells, whereas in AhR-null MEF cells the absence of HDAC2 and the binding of pCREB(Ser133) allow Ltbp-1 transcription. Thus, epigenetics can contribute to constitutive Ltbp-1 repression by a mechanism requiring AhR activity."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2008.04.056"xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Fernandez-Salguero P.M."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Puga A."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Esteller M."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Ballestar E."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Gomez-Duran A."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Carvajal-Gonzalez J.M."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/author | "Marlowe J.L."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/pages | "1-16"xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/title | "Recruitment of CREB1 and histone deacetylase 2 (HDAC2) to the mouse Ltbp-1 promoter regulates its constitutive expression in a dioxin receptor-dependent manner."xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://purl.uniprot.org/core/volume | "380"xsd:string |
| http://purl.uniprot.org/citations/18508077 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18508077 |
| http://purl.uniprot.org/citations/18508077 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18508077 |
| http://purl.uniprot.org/uniprot/#_A0A0B4J1L1-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_A0A087WRI6-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J008-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_A0A3Q4EGK3-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_A0A3Q4L384-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_B1B1E2-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_Q62347-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |
| http://purl.uniprot.org/uniprot/#_Q3U2B1-mappedCitation-18508077 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18508077 |