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Article

Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
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Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1440; https://doi.org/10.3390/cancers11101440
Received: 30 August 2019 / Revised: 19 September 2019 / Accepted: 23 September 2019 / Published: 26 September 2019
(This article belongs to the Special Issue New Insights into Breast and Endometrial Cancer)
The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer–promoter interactions, a mechanism through which GWAS variation may target genes, we captured chromatin loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their targeting. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from normal and tumoral endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes. View Full-Text
Keywords: endometrial cancer risk; GWAS; HiChIP; H3K27Ac; chromatin looping; enhancer; promoter endometrial cancer risk; GWAS; HiChIP; H3K27Ac; chromatin looping; enhancer; promoter
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MDPI and ACS Style

O’Mara, T.A.; Spurdle, A.B.; Glubb, D.M.; Endometrial Cancer Association Consortium. Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci. Cancers 2019, 11, 1440. https://doi.org/10.3390/cancers11101440

AMA Style

O’Mara TA, Spurdle AB, Glubb DM, Endometrial Cancer Association Consortium. Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci. Cancers. 2019; 11(10):1440. https://doi.org/10.3390/cancers11101440

Chicago/Turabian Style

O’Mara, Tracy A., Amanda B. Spurdle, Dylan M. Glubb, and Endometrial Cancer Association Consortium. 2019. "Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci" Cancers 11, no. 10: 1440. https://doi.org/10.3390/cancers11101440

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