Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/264894
Title:
Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.
Authors:
Terrados, Gloria; Finkernagel, Florian; Stielow, Bastian; Sadic, Dennis; Neubert, Juliane; Herdt, Olga; Krause, Michael; Scharfe, Maren; Jarek, Michael; Suske, Guntram
Abstract:
The transcription factor Sp2 is essential for early mouse development and for proliferation of mouse embryonic fibroblasts in culture. Yet its mechanisms of action and its target genes are largely unknown. In this study, we have combined RNA interference, in vitro DNA binding, chromatin immunoprecipitation sequencing and global gene-expression profiling to investigate the role of Sp2 for cellular functions, to define target sites and to identify genes regulated by Sp2. We show that Sp2 is important for cellular proliferation that it binds to GC-boxes and occupies proximal promoters of genes essential for vital cellular processes including gene expression, replication, metabolism and signalling. Moreover, we identified important key target genes and cellular pathways that are directly regulated by Sp2. Most significantly, Sp2 binds and activates numerous sequence-specific transcription factor and co-activator genes, and represses the whole battery of cholesterol synthesis genes. Our results establish Sp2 as a sequence-specific regulator of vitally important genes.
Affiliation:
Institute of Molecular Biology and Tumor Research, Philipps-University, Emil-Mannkopff-Str. 2, D-35032 Marburg, Germany.
Citation:
Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes. 2012, 40 (16):7844-57 Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
Sep-2012
URI:
http://hdl.handle.net/10033/264894
DOI:
10.1093/nar/gks544
PubMed ID:
22684502
Type:
Article
Language:
en
ISSN:
1362-4962
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorTerrados, Gloriaen_GB
dc.contributor.authorFinkernagel, Florianen_GB
dc.contributor.authorStielow, Bastianen_GB
dc.contributor.authorSadic, Dennisen_GB
dc.contributor.authorNeubert, Julianeen_GB
dc.contributor.authorHerdt, Olgaen_GB
dc.contributor.authorKrause, Michaelen_GB
dc.contributor.authorScharfe, Marenen_GB
dc.contributor.authorJarek, Michaelen_GB
dc.contributor.authorSuske, Guntramen_GB
dc.date.accessioned2013-01-11T10:09:50Z-
dc.date.available2013-01-11T10:09:50Z-
dc.date.issued2012-09-
dc.identifier.citationGenome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes. 2012, 40 (16):7844-57 Nucleic Acids Res.en_GB
dc.identifier.issn1362-4962-
dc.identifier.pmid22684502-
dc.identifier.doi10.1093/nar/gks544-
dc.identifier.urihttp://hdl.handle.net/10033/264894-
dc.description.abstractThe transcription factor Sp2 is essential for early mouse development and for proliferation of mouse embryonic fibroblasts in culture. Yet its mechanisms of action and its target genes are largely unknown. In this study, we have combined RNA interference, in vitro DNA binding, chromatin immunoprecipitation sequencing and global gene-expression profiling to investigate the role of Sp2 for cellular functions, to define target sites and to identify genes regulated by Sp2. We show that Sp2 is important for cellular proliferation that it binds to GC-boxes and occupies proximal promoters of genes essential for vital cellular processes including gene expression, replication, metabolism and signalling. Moreover, we identified important key target genes and cellular pathways that are directly regulated by Sp2. Most significantly, Sp2 binds and activates numerous sequence-specific transcription factor and co-activator genes, and represses the whole battery of cholesterol synthesis genes. Our results establish Sp2 as a sequence-specific regulator of vitally important genes.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Nucleic acids researchen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBase Sequenceen_GB
dc.subject.meshBinding Sitesen_GB
dc.subject.meshCell Proliferationen_GB
dc.subject.meshDNAen_GB
dc.subject.meshData Miningen_GB
dc.subject.meshGene Deletionen_GB
dc.subject.meshGene Expression Profilingen_GB
dc.subject.meshGene Expression Regulationen_GB
dc.subject.meshGenomeen_GB
dc.subject.meshHEK293 Cellsen_GB
dc.subject.meshHeLa Cellsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMiceen_GB
dc.subject.meshPosition-Specific Scoring Matricesen_GB
dc.subject.meshPromoter Regions, Geneticen_GB
dc.subject.meshRNA Interferenceen_GB
dc.subject.meshSp1 Transcription Factoren_GB
dc.subject.meshSp2 Transcription Factoren_GB
dc.titleGenome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.en
dc.typeArticleen
dc.contributor.departmentInstitute of Molecular Biology and Tumor Research, Philipps-University, Emil-Mannkopff-Str. 2, D-35032 Marburg, Germany.en_GB
dc.identifier.journalNucleic acids researchen_GB
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