Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.
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.
Institute of Molecular Biology and Tumor Research, Philipps-University, Emil-Mannkopff-Str. 2, D-35032 Marburg, Germany.
Gloria
G
Terrados
Florian
F
Finkernagel
Bastian
B
Stielow
Dennis
D
Sadic
Juliane
J
Neubert
Olga
O
Herdt
Michael
M
Krause
Maren
M
Scharfe
Michael
M
Jarek
Guntram
G
Suske
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D057225:Data Mining; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D056510:Position-Specific Scoring Matrices; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051704:Sp2 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D016329:Sp1 Transcription Factor; D051704:Sp2 Transcription Factor; D004247:DNA