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Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.
Terrados, Gloria Finkernagel, Florian Stielow, Bastian Sadic, Dennis Neubert, Juliane Herdt, Olga Krause, Michael Scharfe, Maren Jarek, Michael Suske, Guntram
Terrados, Gloria
Finkernagel, Florian
Stielow, Bastian
Sadic, Dennis
Neubert, Juliane
Herdt, Olga
Krause, Michael
Scharfe, Maren
Jarek, Michael
Suske, Guntram
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2012-09
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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.
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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.
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en
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1362-4962
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Archived with thanks to Nucleic acids research