Identification of genes directly regulated by the oncogene ZNF217 using chromatin immunoprecipitation (ChIP)-chip assays.
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.
Krig
Sheryl R
SR
Department of Pharmacology and the Genome Center, University of California, Davis, California 95616.
Jin
Victor X
VX
Department of Pharmacology and the Genome Center, University of California, Davis, California 95616.
Bieda
Mark C
MC
Department of Pharmacology and the Genome Center, University of California, Davis, California 95616.
O'Geen
Henriette
H
Department of Pharmacology and the Genome Center, University of California, Davis, California 95616.
Yaswen
Paul
P
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Green
Roland
R
NimbleGen Systems Inc., Madison, Wisconsin 53711.
Farnham
Peggy J
PJ
Department of Pharmacology and the Genome Center, University of California, Davis, California 95616. Electronic address: pjfarnham@ucdavis.edu.
D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D016335:Zinc Fingers / Q000235:genetics
D015534:Trans-Activators; C113698:ZNF217 protein, human