The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Upregulation of c- MYC in cis through a Large Chromatin Loop Linked to a Cancer Risk-Associated Single-Nucleotide Polymorphism in Colorectal Cancer Cells
Open accessAbstract
Genome-wide association studies have mapped many single-nucleotide polymorphisms (SNPs) that are linked to cancer risk, but the mechanism by which most SNPs promote cancer remains undefined. The rs6983267 SNP at 8q24 has been associated with many cancers, yet the SNP falls 335 kb from the nearest gene, c-MYC. We show that the beta-catenin-TCF4 transcription factor complex binds preferentially to the cancer risk-associated rs6983267(G) allele in colon cancer cells. We also show that the rs6983267 SNP has enhancer-related histone marks and can form a 335-kb chromatin loop to interact with the c-MYC promoter. Finally, we show that the SNP has no effect on the efficiency of chromatin looping to the c-MYC promoter but that the cancer risk-associated SNP enhances the expression of the linked c-MYC allele. Thus, cancer risk is a direct consequence of elevated c-MYC expression from increased distal enhancer activity and not from reorganization/creation of the large chromatin loop. The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops.
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Cites
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BackgroundHistone modifications at human enhancers reflect global cell-type-specific gene expression
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Cited by
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The many faces and functions of β‐catenin
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Exploring the three-dimensional organization of genomes: Interpreting chromatin interaction data
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Beyond GWASs: Illuminating the Dark Road from Association to Function
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Metadata
- Authors
- Wright, J. B., Brown, S. J., & Cole, M. D.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2010-03
- Volume
- 30
- Issue
- 6
- Pages
- 1411-1420
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2057629607
- Cited by
- 258
- References
- 9
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- green
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