The PAX8 cistrome in epithelial ovarian cancer

Oncotarget
Emily K AdlerSimon A Gayther

Abstract

PAX8 is a lineage-restricted transcription factor that is expressed in epithelial ovarian cancer (EOC) precursor tissues, and in the major EOC histotypes. Frequent overexpression of PAX8 in primary EOCs suggests this factor functions as an oncogene during tumorigenesis, however, the biological role of PAX8 in EOC development is poorly understood. We found that stable knockdown of PAX8 in EOC models significantly reduced cell proliferation and anchorage dependent growth in vitro, and attenuated tumorigenicity in vivo. Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and transcriptional profiling were used to create genome-wide maps of PAX8 binding and putative target genes. PAX8 binding sites were significantly enriched in promoter regions (p < 0.05) and superenhancers (p < 0.05). MEME-ChIP analysis revealed that PAX8 binding sites overlapping superenhancers or enhancers, but not promoters, were enriched for JUND/B and ARNT/AHR motifs. Integrating PAX8 ChIP-seq and gene expression data identified PAX8 target genes through their associations within shared topological association domains. Across two EOC models we identified 62 direct regulatory targets based on PAX8 binding in promoters and 1,330 put...Continue Reading

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Aug 23, 2019·Nature Communications·Melusine BleuGiorgio G Galli
Dec 14, 2019·Cancer Cell International·Amata Amy SorianoMariastella Zannini
Apr 26, 2020·Nature Communications·Rosario I CoronaKate Lawrenson
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Apr 28, 2021·Nature Communications·Melusine BleuGiorgio Giacomo Galli
Nov 25, 2021·Science Advances·Jessica ReddyKate Lawrenson

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Methods Mentioned

BETA
xenograft
immunoprecipitation
ChIP-seq
acetylation
biopsies
Assay
PCR
immunoprecipitations

Software Mentioned

ChIP
Bioconductor
ChIP suite
MACS2
BWA
HOMER
IDR
Metascape
R
MEME

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