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Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha

BACKGROUND: The ZNF217 gene, encoding a C(2)H(2) 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 asso...

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Autores principales: Frietze, Seth, O’Geen, Henriette, Littlepage, Laurie E, Simion, Catalina, Sweeney, Colleen A, Farnham, Peggy J, Krig, Sheryl R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082627/
https://www.ncbi.nlm.nih.gov/pubmed/24962896
http://dx.doi.org/10.1186/1471-2164-15-520
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author Frietze, Seth
O’Geen, Henriette
Littlepage, Laurie E
Simion, Catalina
Sweeney, Colleen A
Farnham, Peggy J
Krig, Sheryl R
author_facet Frietze, Seth
O’Geen, Henriette
Littlepage, Laurie E
Simion, Catalina
Sweeney, Colleen A
Farnham, Peggy J
Krig, Sheryl R
author_sort Frietze, Seth
collection PubMed
description BACKGROUND: The ZNF217 gene, encoding a C(2)H(2) 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 ChIP-seq 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 cis-regulatory 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. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-520) contains supplementary material, which is available to authorized users.
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spelling pubmed-40826272014-07-18 Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha Frietze, Seth O’Geen, Henriette Littlepage, Laurie E Simion, Catalina Sweeney, Colleen A Farnham, Peggy J Krig, Sheryl R BMC Genomics Research Article BACKGROUND: The ZNF217 gene, encoding a C(2)H(2) 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 ChIP-seq 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 cis-regulatory 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. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-520) contains supplementary material, which is available to authorized users. BioMed Central 2014-06-24 /pmc/articles/PMC4082627/ /pubmed/24962896 http://dx.doi.org/10.1186/1471-2164-15-520 Text en © Frietze et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Frietze, Seth
O’Geen, Henriette
Littlepage, Laurie E
Simion, Catalina
Sweeney, Colleen A
Farnham, Peggy J
Krig, Sheryl R
Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title_full Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title_fullStr Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title_full_unstemmed Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title_short Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha
title_sort global analysis of znf217 chromatin occupancy in the breast cancer cell genome reveals an association with eralpha
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082627/
https://www.ncbi.nlm.nih.gov/pubmed/24962896
http://dx.doi.org/10.1186/1471-2164-15-520
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