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E-GEOD-21495 - Genome wide screen reveals WNT11, a noncanonical WNT gene, as a target of ETS transcription factor ERG

Status
Released on 10 December 2010, last updated on 1 May 2014
Organism
Homo sapiens
Samples (16)
Arrays (2)
Protocols (13)
Description
ERG is a transcription factor that is involved in leukomogenesis and its mRNA overexpression has been associated with poor prognosis in a subset of patients with T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Herein, a genome-wide screen of ERG target genes was conducted by chromatin immunoprecipitation-on-chip (ChIP-chip) in Jurkat cells. 342 significant annotated regions were derived from ChIP-chip experiments. Seventeen candidate promoter regions resulted in at least two-fold enrichment by quantitative PCR. Notably, ERG potential targets included WNT signaling genes: WNT2, WNT9A, WNT11, CCND1, and FZD7. Functionally, expression of WNT11 was downregulated with siRNA ERG knockdown and substantially upregulated in a tet-on ERG-inducible assay in K562 cells. To investigate a role for ERG in WNT signaling, a WNT agonist was used to inhibit glycogen synthase kinase (GSK-3). This treatment resulted in an ERG-dependent proliferative growth advantage in the tet-on ERG-inducible system. Lastly, chromatin immunoprecipitation assays of primary leukemia blasts confirmed WNT11 promoter enrichment dependent on ERG mRNA expression. In conclusion, ERG transcriptional networks in leukemia are revealed. Specifically, WNT11 emerged as a target of ERG. We propose that overexpression of ERG in acute leukemia may lead to a proliferative advantage upon activation of WNT signals. ChIP-chip with ERG antibody C20 and combined C17/20 and nonspecificic IgG in Jurkat
Experiment type
ChIP-chip by tiling array 
Contacts
Liliana H. Mochmann <liliana.mochmann@charite.de>, Arend Bohne, Claudia D Baldus, Cornelia Schlee, Eckhard Thiel, Juliane Bock, Jutta Ortiz-Tanchez, Konrad Neumann, Liliana H Mochmann, Wolf K Hofmann
MIAME
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