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Int. J. Mol. Sci. 2018, 19(5), 1458; https://doi.org/10.3390/ijms19051458

Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1

1
Department of Biomedical Sciences, University of Ulsan School of Medicine, Asan Medical Center, Seoul 05505, Korea
2
Department of Physiology, University of Ulsan School of Medicine, Asan Medical Center, Seoul 05505, Korea
3
Department of Microbiology, College of Natural Sciences, Dankook University, Cheonan 31116, Korea
4
Cancer Research Institute, Catholic University of Korea, Seoul 06591, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 9 April 2018 / Revised: 26 April 2018 / Accepted: 11 May 2018 / Published: 14 May 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

BRCA1 is a multifunctional tumor suppressor involved in several essential cellular processes. Although many of these functions are driven by or related to its transcriptional/epigenetic regulator activity, there has been no genome-wide study to reveal the transcriptional/epigenetic targets of BRCA1. Therefore, we conducted a comprehensive analysis of genomics/transcriptomics data to identify novel BRCA1 target genes. We first analyzed ENCODE data with BRCA1 chromatin immunoprecipitation (ChIP)-sequencing results and identified a set of genes with a promoter occupied by BRCA1. We collected 3085 loci with a BRCA1 ChIP signal from four cell lines and calculated the distance between the loci and the nearest gene transcription start site (TSS). Overall, 66.5% of the BRCA1-bound loci fell into a 2-kb region around the TSS, suggesting a role in transcriptional regulation. We selected 45 candidate genes based on gene expression correlation data, obtained from two GEO (Gene Expression Omnibus) datasets and TCGA data of human breast cancer, compared to BRCA1 expression levels. Among them, we further tested three genes (MEIS2, CKS1B and FADD) and verified FADD as a novel direct target of BRCA1 by ChIP, RT-PCR, and a luciferase reporter assay. Collectively, our data demonstrate genome-wide transcriptional regulation by BRCA1 and suggest target genes as biomarker candidates for BRCA1-associated breast cancer. View Full-Text
Keywords: BRCA1; ENCODE; ChIP-seq; GEO; FADD BRCA1; ENCODE; ChIP-seq; GEO; FADD
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Nguyen, D.-D.; Lee, D.G.; Kim, S.; Kang, K.; Rhee, J.-K.; Chang, S. Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1. Int. J. Mol. Sci. 2018, 19, 1458.

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