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

International Journal of Molecular Sciences
Dinh-Duc NguyenSuhwan Chang

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 as...Continue Reading

References

Aug 22, 1996·Nature·M S Chapman, I M Verma
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·A N MonteiroH Hanafusa
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·R ScullyJ D Parvin
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·R I Yarden, L C Brody
Aug 12, 2000·The Journal of Biological Chemistry·M ThangarajuF J Couch
Aug 30, 2000·Oncogene·S JinQ Zhan
Aug 9, 2001·Proceedings of the National Academy of Sciences of the United States of America·L ZhengT G Boyer
Jan 5, 2002·The Journal of Biological Chemistry·Wenhong FanQimin Zhan
Jun 26, 2002·The Journal of Biological Chemistry·Ying YanKenneth H Cowan
Apr 18, 2003·The Journal of Biological Chemistry·Miriam BenezraJonathan D Licht
Mar 5, 2004·Journal of Clinical Immunology·Sudhir GuptaSastry Gollapudi
Oct 23, 2004·Science·UNKNOWN ENCODE Project Consortium
Feb 14, 2007·The Oncologist·Colin R JamesD Paul Harkin
Sep 29, 2011·Nature Medicine·Suhwan ChangShyam K Sharan
Dec 15, 2011·Breast Cancer Research and Treatment·Miljana TanicBeatriz Martínez-Delgado
Mar 10, 2012·Oncotarget·Suhwan Chang, Shyam K Sharan
Jun 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James L ChenDonald J Vander Griend
Nov 30, 2012·Nucleic Acids Research·Tanya BarrettAlexandra Soboleva
Dec 19, 2014·BMC Cancer·Chirayu Pankaj Goswami, Harikrishna Nakshatri

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Citations

Jun 21, 2019·Laboratory Medicine·Narges AnsariHadi Rezaeean
Oct 2, 2019·Cancers·José L Marín-RubioMaría Villa-Morales

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Datasets Mentioned

BETA
GM12878
GSE30822
GSE22259

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
ChIP
transfections
Assay
transfection
PCR

Software Mentioned

image J
PROGgen
PROGgeneV2

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