Identification of PBX1 target genes in cancer cells by global mapping of PBX1 binding sites.

PloS One
Michelle M ThiavilleTian-Li Wang

Abstract

PBX1 is a TALE homeodomain transcription factor involved in organogenesis and tumorigenesis. Although it has been shown that ovarian, breast, and melanoma cancer cells depend on PBX1 for cell growth and survival, the molecular mechanism of how PBX1 promotes tumorigenesis remains unclear. Here, we applied an integrated approach by overlapping PBX1 ChIP-chip targets with the PBX1-regulated transcriptome in ovarian cancer cells to identify genes whose transcription was directly regulated by PBX1. We further determined if PBX1 target genes identified in ovarian cancer cells were co-overexpressed with PBX1 in carcinoma tissues. By analyzing TCGA gene expression microarray datasets from ovarian serous carcinomas, we found co-upregulation of PBX1 and a significant number of its direct target genes. Among the PBX1 target genes, a homeodomain protein MEOX1 whose DNA binding motif was enriched in PBX1-immunoprecipicated DNA sequences was selected for functional analysis. We demonstrated that MEOX1 protein interacts with PBX1 protein and inhibition of MEOX1 yields a similar growth inhibitory phenotype as PBX1 suppression. Furthermore, ectopically expressed MEOX1 functionally rescued the PBX1-withdrawn effect, suggesting MEOX1 mediates the...Continue Reading

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Citations

Mar 23, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Francesco BlasiLeila Dardaei
Jan 18, 2017·Scientific Reports·Chiara ZucchelliChiara Bruckmann
Mar 5, 2017·Molecular Immunology·Yuxin NiuLaurence Morel
Mar 7, 2017·International Journal of Cancer. Journal International Du Cancer·Jun WangSeema A Khan
Sep 18, 2015·The Journal of Biological Chemistry·Leonardo BeccariPaola Bovolenta
Dec 14, 2018·Cancer Biotherapy & Radiopharmaceuticals·Zhi-Yuan ZhuDa-Peng Li
Sep 16, 2018·Genome Biology·Yungang XuXiaobo Zhou
Jul 29, 2015·Molecular Endocrinology·Tara L ConfortoDavid J Waxman
Mar 29, 2020·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Yier QiuYingjie Wu
Mar 7, 2017·Frontiers in Cell and Developmental Biology·Britta M Grebbin, Dorothea Schulte
Nov 3, 2016·Cancer Research·Jin-Gyoung JungTian-Li Wang
Sep 17, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Rafaela Nasser VeigaDaniela Fiori Gradia

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Methods Mentioned

BETA
ChIP-chip
ChIP
immunoprecipitation
PCR
co-immunoprecipitation
pull-down
transfection

Software Mentioned

Cistrome
R
GenomicRanges
Primer
iCycler Optical
NimbleGen
iCycler Optical system
Bioconductor package
CGDS
Signal Map

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