Identification of Genes Directly Regulated by the Oncogene ZNF217 Using Chromatin Immunoprecipitation (ChIP)-Chip Assays

Krig, Sheryl R.; Jin, Victor X.; Bieda, Mark; O’Geen, Henriette; Yaswen, Paul; Green, Roland; Farnham, Peggy J.

doi:10.1074/jbc.m611752200

Cited by 73 publications

(93 citation statements)

References 40 publications

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“…Other mechanisms, such as mutations or aberrant methylation, may suppress the expression of CXXC4 during the progression of RCC. Recently, CXXC4 was revealed to be one of several genes downregulated by ZNF217 binding (Krig et al, 2007). Thus, transcriptional regulation could be a mechanism to suppress the expression of CXXC4.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

et al. 2008

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The Wnt signaling pathway is involved in normal embryonic development and controls the homeostatic self-renewal of stem cells in adult tissues. Constitutive activation of Wnt signaling contributes to cancer development and progression. We identified a CXXC4 homozygous deletion at 4q24 in an aggressive renal cell carcinoma (RCC) using single-nucleotide polymorphism (SNP) arrays. CXXC4 encodes Idax, which negatively regulates Wnt signaling by binding to the PDZ domain of Dishevelled. CXXC4 mRNA levels in tumor samples were significantly lower in patients with metastases compared with those without (P ¼ 0.0016). Patients whose tumors had lower CXXC4 expression than normal kidney showed a poorer cause-specific survival outcome than those with higher expression (P ¼ 0.0095). Decreased expression of CXXC4 also correlated with cytoplasmic staining of b-catenin. Knockdown of CXXC4 induced the nuclear translocation of b-catenin and altered expression of a set of genes involved in cell proliferation, invasion and survival. Furthermore, reduced expression of CXXC4 by small interfering RNAs promoted cell proliferation and inhibited apoptosis after 5-FU and doxorubicin treatment in RCC cells. These data suggest that CXXC4 plays a critical role in tumor progression of RCC through Wnt signaling. Wnt signaling could thus be a potential molecular target in RCC indicating decreased CXXC4 expression.

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Section: Discussionmentioning

confidence: 99%

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

et al. 2008

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“…ZNF217 is a Kr€ uppel-like zinc finger protein that localizes to the nucleus (4) and interacts with corepressors and histonemodifying proteins, suggesting that it may be part of a transcriptional repressor complex (5)(6)(7). However, the role of ZNF217 in transcriptional regulation is likely to be complex, as ZNF217 has also been shown to induce positive transcriptional regulation of target genes (8,9). Previous studies have found that high levels of ZNF217 expression have been associated with resistance to chemotherapy and with deregulated apoptotic signals in breast cancer cells (10,11).…”

Section: Introductionmentioning

confidence: 99%

“…We then carried out ChIP experiments on several ZNF217-binding sites (6,8) found in the À5 Kb to þ1 Kb promoter region of the TGFB1, TGFB2, and TGFB3 genes (Supplementary Table S3). PCR amplification of the TGFB2-P4 and the TGFB3-P1 regions was observed in the MCF10A-ZNF217 cells and not in control cells (Fig.…”

Section: Znf217 Promotes Emt In Mammary Epithelial Cellsmentioning

confidence: 99%

ZNF217 Is a Marker of Poor Prognosis in Breast Cancer That Drives Epithelial–Mesenchymal Transition and Invasion

et al. 2012

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The Kr€ uppel-like zinc finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we showed that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo. ZNF217 also promoted epithelial-mesenchymal transition (EMT) in human mammary epithelial cells, and the TGF-b-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-b autocrine loop sustained activation of the TGF-b pathway in ZNF217-overexpressing mammary epithelial cells, most likely because of ZNF217-mediated direct upregulation of TGFB2 or TGFB3. Inhibition of the TGF-b pathway led to the reversal of ZNF217-mediated EMT. Together, our findings indicate that ZNF217 mRNA expression may represent a novel prognostic biomarker in breast cancer. Therapeutic targeting of ZNF217 of the TGF-b signaling pathway may benefit the subset of patients whose tumors express high levels of ZNF217. Cancer Res; 72(14); 3593-606. Ó2012 AACR.

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“…Genome-wide transcription factor occupancy techniques, such as chromatin immunoprecipitation (ChIP) coupled with DNA microarrays (termed ChIP-chip), can define transcription factor in vivo utilization of genomic sequences and inform bioinformatics approaches. However, most genome-wide occupancy studies in mammalian systems have failed to identify matches to in vitro consensus binding sequences in the majority of occupied regions (Weinmann et al 2002;Li et al 2003;Martone et al 2003;Euskirchen et al 2004;Krig et al 2007). In addition, recognizable consensus sites can display no evidence of binding.…”

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confidence: 99%

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

et al. 2007

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The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within the ETS gene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found-a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family.[Keywords: ETS; transcription; gene families; cooperative binding; promoter specificity; ChIP-chip] Supplemental material is available at www.genesdev.org.

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Identification of Genes Directly Regulated by the Oncogene ZNF217 Using Chromatin Immunoprecipitation (ChIP)-Chip Assays

Cited by 73 publications

References 40 publications

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

ZNF217 Is a Marker of Poor Prognosis in Breast Cancer That Drives Epithelial–Mesenchymal Transition and Invasion

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

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