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Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes
IRF1 is a transcription factor involved in interferon signaling and has been shown to harbor tumor suppressor activity. In order to comprehensively identify pathways regulated by IRF1, we used chromatin immunoprecipitation followed by massive-parallel sequencing (ChIP-seq) to evaluate the gene targe...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398980/ https://www.ncbi.nlm.nih.gov/pubmed/25893139 http://dx.doi.org/10.4172/2157-2518.S6-009 |
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author | Rettino, Alessandro Clarke, Nicole M |
author_facet | Rettino, Alessandro Clarke, Nicole M |
author_sort | Rettino, Alessandro |
collection | PubMed |
description | IRF1 is a transcription factor involved in interferon signaling and has been shown to harbor tumor suppressor activity. In order to comprehensively identify pathways regulated by IRF1, we used chromatin immunoprecipitation followed by massive-parallel sequencing (ChIP-seq) to evaluate the gene targets of IRF1 genome-wide. We identified 17,416 total binding events in breast cancer cells. Functional categorization of the binding sites after IFN-gamma (interferon-gamma) treatment determined that ‘apoptosis’ or ‘cell death’ is the most enriched target process. Motif discovery analysis of the chromosomal regions bound by IRF1 identified a number of unique motifs correlated with apoptosis, DNA damage and immune processes. Analysis of GEO transcriptome data from IRF1-transduced cells or IFN-gamma treated fibroblasts indicates that IRF1-bound targets in IFN-treated cells are associated with a positive transcriptional response. Many of the enriched target genes from the expression analysis are associated with apoptosis. Importantly, this data indicates that a significant function of IRF1 is the regulation of anti-cancer apoptotic pathways and this reinforces IRF1’s role as a tumor suppressor. |
format | Online Article Text |
id | pubmed-4398980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43989802015-04-16 Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes Rettino, Alessandro Clarke, Nicole M J Carcinog Mutagen Article IRF1 is a transcription factor involved in interferon signaling and has been shown to harbor tumor suppressor activity. In order to comprehensively identify pathways regulated by IRF1, we used chromatin immunoprecipitation followed by massive-parallel sequencing (ChIP-seq) to evaluate the gene targets of IRF1 genome-wide. We identified 17,416 total binding events in breast cancer cells. Functional categorization of the binding sites after IFN-gamma (interferon-gamma) treatment determined that ‘apoptosis’ or ‘cell death’ is the most enriched target process. Motif discovery analysis of the chromosomal regions bound by IRF1 identified a number of unique motifs correlated with apoptosis, DNA damage and immune processes. Analysis of GEO transcriptome data from IRF1-transduced cells or IFN-gamma treated fibroblasts indicates that IRF1-bound targets in IFN-treated cells are associated with a positive transcriptional response. Many of the enriched target genes from the expression analysis are associated with apoptosis. Importantly, this data indicates that a significant function of IRF1 is the regulation of anti-cancer apoptotic pathways and this reinforces IRF1’s role as a tumor suppressor. 2013 /pmc/articles/PMC4398980/ /pubmed/25893139 http://dx.doi.org/10.4172/2157-2518.S6-009 Text en Copyright: © 2013 Rettino A, et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Rettino, Alessandro Clarke, Nicole M Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title | Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title_full | Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title_fullStr | Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title_full_unstemmed | Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title_short | Genome-wide Identification of IRF1 Binding Sites Reveals Extensive Occupancy at Cell Death Associated Genes |
title_sort | genome-wide identification of irf1 binding sites reveals extensive occupancy at cell death associated genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398980/ https://www.ncbi.nlm.nih.gov/pubmed/25893139 http://dx.doi.org/10.4172/2157-2518.S6-009 |
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