RNA-seq of wild-type and ZNF217-knockout KOPN-8 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE272398 | GEO | 2025/02/16
REPOSITORIES: GEO
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Project description:Here, we elucidate the oncogenic role of ZNF217 in B-ALL and reveal that ZNF217 interacts with the CoREST complex to mediate histone modifications such as H3K4me1, H3K4me2, and H3K27ac. This interaction partially contributes to ZNF217’s oncogenic function in B-ALL. To identify genes directly bound by ZNF217, we conducted high-throughput CUT&RUN sequencing using an anti-ZNF217 antibody in both wild-type and ZNF217-knockdown KOPN-8 cells. Additionally, to distinguish between CoREST-dependent and CoREST-independent targets, we performed CUT&RUN sequencing in the same cell models using an antibody against LSD1, a core component of the CoREST complex that interacts with ZNF217, as well as antibodies against H3K4me1, H3K4me2, and H3K27ac.
2025-02-16 | GSE272397 | GEO
Project description:We previously identified ZNF217 as an oncogenic driver of a subset of osteosarcomas (OSAs) using the Sleeping Beauty (SB) transposon system. Here, we followed up investigating the role of ZNF217 in OSA and combined these studies with an orthotopic preclinical animal model and culture experiments. We found that targeting ZNF217-induced AKT signaling with a small molecule inhibitor is a promising approach to treating ZNF217+ OSAs. Here, we demonstrate that ZNF217 is involved in numerous facets of OSA transformation including proliferation, cell motility, colony formation, and ultimately promoting OSA growth, progression, and metastasis in part through AKT survival pathway modulation. Preclinical blockade of AKT signaling with nucleoside analogue triciribine (TCN) in ZNF217+ orthotopically-injected OSA cell lines reduced tumor growth, metastasis, and was well-tolerated. TCN treatment was also found to synergize with common broad-spectrum chemotherapeutic doxorubicin. Our data demonstrate that TCN treatment may be a relevant and efficacious therapeutic strategy for OSA patients with ZNF217+ and p-AKTSer473-rich tumors. With the recent revitalization of triciribine for clinical studies in other solid cancers (PTX-200, Prescient Therapeutics), our study provides rationale for further evaluation preclinically with the purpose of clinical evaluation in patients with incurable, ZNF217+ OSA.
2020-03-24 | GSE147413 | GEO
Project description:Background: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance Differential RNA-seq profiling from triplicate biological replicates of MCF7 cells treated with scrambled siRNA or siZNF217.
2014-06-15 | E-GEOD-58326 | biostudies-arrayexpress
Project description:Background: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance
2014-06-15 | GSE58326 | GEO
Project description:It has been proposed that ZNF217, which is amplified at 20q13 in various tumors, plays a key role during neoplastic transformation. ZNF217 has been purified in complexes that contain repressor proteins such as CtBP2, suggesting that it acts as a transcriptional repressor. However, the function of ZNF217 has not been well characterized due to a lack of known target genes. Using a global ChIP-chip approach, we have identified thousands of ZNF217 binding sites in three tumor cell lines (MCF7, SW480, and Ntera2). Further analysis of ZNF217 in Ntera2 cells has shown that many promoters are bound by ZNF217 and CtBP2, and that a subset of these promoters are activated upon removal of ZNF217. Thus, our in vivo studies corroborate the in vitro biochemical analyses of ZNF217-containing complexes and support the hypothesis that ZNF217 functions as transcriptional repressor. Gene ontology analysis shows that ZNF217 targets in Ntera2 cells are involved in organ development, suggesting that one function of ZNF217 may be to repress differentiation. Accordingly, we show that differentiation of Ntera2 cells with retinoic acid leads to downregulation of ZNF217. Our identification of thousands of ZNF217 target genes will enable further studies of the consequences of aberrant expression of ZNF217 during neoplastic transformation. Keywords: ChIP-chip
2007-01-25 | GSE6624 | GEO
Project description:It has been proposed that ZNF217, which is amplified at 20q13 in various tumors, plays a key role during neoplastic transformation. ZNF217 has been purified in complexes that contain repressor proteins such as CtBP2, suggesting that it acts as a transcriptional repressor. However, the function of ZNF217 has not been well characterized due to a lack of known target genes. Using a global ChIP-chip approach, we have identified thousands of ZNF217 binding sites in three tumor cell lines (MCF7, SW480, and Ntera2). Further analysis of ZNF217 in Ntera2 cells has shown that many promoters are bound by ZNF217 and CtBP2, and that a subset of these promoters are activated upon removal of ZNF217. Thus, our in vivo studies corroborate the in vitro biochemical analyses of ZNF217-containing complexes and support the hypothesis that ZNF217 functions as transcriptional repressor. Gene ontology analysis shows that ZNF217 targets in Ntera2 cells are involved in organ development, suggesting that one function of ZNF217 may be to repress differentiation. Accordingly, we show that differentiation of Ntera2 cells with retinoic acid leads to downregulation of ZNF217. Our identification of thousands of ZNF217 target genes will enable further studies of the consequences of aberrant expression of ZNF217 during neoplastic transformation. ChIP-chip assays on Promoter arrays using anti-ZNF217
2010-06-12 | E-GEOD-6625 | biostudies-arrayexpress
Project description:It has been proposed that ZNF217, which is amplified at 20q13 in various tumors, plays a key role during neoplastic transformation. ZNF217 has been purified in complexes that contain repressor proteins such as CtBP2, suggesting that it acts as a transcriptional repressor. However, the function of ZNF217 has not been well characterized due to a lack of known target genes. Using a global ChIP-chip approach, we have identified thousands of ZNF217 binding sites in three tumor cell lines (MCF7, SW480, and Ntera2). Further analysis of ZNF217 in Ntera2 cells has shown that many promoters are bound by ZNF217 and CtBP2, and that a subset of these promoters are activated upon removal of ZNF217. Thus, our in vivo studies corroborate the in vitro biochemical analyses of ZNF217-containing complexes and support the hypothesis that ZNF217 functions as transcriptional repressor. Gene ontology analysis shows that ZNF217 targets in Ntera2 cells are involved in organ development, suggesting that one function of ZNF217 may be to repress differentiation. Accordingly, we show that differentiation of Ntera2 cells with retinoic acid leads to downregulation of ZNF217. Our identification of thousands of ZNF217 target genes will enable further studies of the consequences of aberrant expression of ZNF217 during neoplastic transformation. Keywords: mRNA Expression
2007-01-25 | GSE6627 | GEO
Project description:It has been proposed that ZNF217, which is amplified at 20q13 in various tumors, plays a key role during neoplastic transformation. ZNF217 has been purified in complexes that contain repressor proteins such as CtBP2, suggesting that it acts as a transcriptional repressor. However, the function of ZNF217 has not been well characterized due to a lack of known target genes. Using a global ChIP-chip approach, we have identified thousands of ZNF217 binding sites in three tumor cell lines (MCF7, SW480, and Ntera2). Further analysis of ZNF217 in Ntera2 cells has shown that many promoters are bound by ZNF217 and CtBP2, and that a subset of these promoters are activated upon removal of ZNF217. Thus, our in vivo studies corroborate the in vitro biochemical analyses of ZNF217-containing complexes and support the hypothesis that ZNF217 functions as transcriptional repressor. Gene ontology analysis shows that ZNF217 targets in Ntera2 cells are involved in organ development, suggesting that one function of ZNF217 may be to repress differentiation. Accordingly, we show that differentiation of Ntera2 cells with retinoic acid leads to downregulation of ZNF217. Our identification of thousands of ZNF217 target genes will enable further studies of the consequences of aberrant expression of ZNF217 during neoplastic transformation. Keywords: ChIP-chip
2007-01-25 | GSE6625 | GEO
Project description:To obtain an overview of the cellular functions regulated by ZNF217 signaling in breast-cancer cell lines, we performed global gene-expression profiling on MDA-MB-231-pcDNA6 and MDA-MB-231-ZNF217 cells
2012-02-06 | GSE35511 | GEO
Project description:The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20-30% of primary human breast cancers and that correlates with poor prognosis. We show Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We demonstrate that the nucleoside analog triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance, and inhibits signaling events (e.g., P-AKT, P-MAPK) in vivo. Our data suggest ZNF217 is a biomarker of poor prognosis and a therapeutic target in breast cancer patients, and triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Since ZNF217 is amplified in numerous cancers, these results have implications for other cancers.
2012-05-18 | GSE24727 | GEO