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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
Identification of genes directly regulated by the oncogene ZNF217 using chromatin immunoprecipitation (ChIP)-chip
Sheryl R Krig1, Victor X Jin1, Mark C Bieda1
1Department of Pharmacology and the Genome Center, University of California, Davis, California 95616.
Abstract:
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 chromatin immunoprecipitation (ChIP)-chip approach, we identified thousands of ZNF217 binding sites in three tumor cell lines (MCF7, SW480, and Ntera2). Further analysis of ZNF217 in Ntera2 cells showed 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 a transcriptional repressor. Gene ontology analysis showed 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 led to down-regulation 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.
Insights
Zinc finger protein 217 (ZNF217) acts as a transcriptional repressor, potentially inhibiting cell differentiation during cancer development. This study identifies thousands of ZNF217 target genes, offering new insights into its role in neoplastic transformation.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- The ZNF217 gene is amplified in various tumors and implicated in neoplastic transformation.
- ZNF217 has been associated with repressor proteins like CtBP2, suggesting a role in transcriptional repression.
- The precise function of ZNF217 remains unclear due to a lack of identified target genes.
Purpose of the Study:
- To identify ZNF217 target genes using a global approach.
- To investigate the in vivo function of ZNF217 as a transcriptional repressor.
- To explore the role of ZNF217 in cell differentiation and neoplastic transformation.
Main Methods:
- Chromatin immunoprecipitation (ChIP)-chip assays were performed on three tumor cell lines (MCF7, SW480, Ntera2).
- ZNF217 and CtBP2 binding sites were analyzed at promoters in Ntera2 cells.
- Gene ontology analysis was used to determine the function of ZNF217 target genes.
- Retinoic acid was used to induce differentiation in Ntera2 cells to observe ZNF217 expression changes.
Main Results:
- Thousands of ZNF217 binding sites were identified across the genome in the studied cell lines.
- A subset of ZNF217 and CtBP2 co-bound promoters were activated upon ZNF217 removal, supporting its repressor function.
- ZNF217 targets are enriched in pathways related to organ development, suggesting a role in repressing differentiation.
- Differentiation of Ntera2 cells with retinoic acid resulted in decreased ZNF217 expression.
Conclusions:
- The study confirms ZNF217 functions as a transcriptional repressor in vivo.
- ZNF217 may play a role in preventing cell differentiation, contributing to neoplastic transformation.
- The identified ZNF217 target genes provide a foundation for future research into its oncogenic functions.
