Chromatin structure is distinct between coding and non-coding single nucleotide polymorphisms

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Previous studies suggested that nucleosomes are enriched with single nucleotide polymorphisms (SNPs) in humans and that the occurrence of mutations is closely associated with CpG dinucleotides. We aimed to determine if the chromatin organization is genomic locus specific around SNPs, and if newly occurring mutations are associated with SNPs. Results: Here, we classified SNPs according their loci and investigated chromatin organization in both CD4 T cell and lymphoblastoid cell in humans. We calculated the SNP frequency around somatic mutations. The results indicated that nucleosome occupancy is different around SNPs sites in different genomic loci. Coding SNPs are mainly enriched at nucleosomes and associated with repressed histone modifications (HMs) and DNA methylation. Contrastingly, intron SNPs occur in nucleosome-depleted regions and lack HMs. Interestingly, risk-associated non-coding SNPs are also enriched at nucleosomes with HMs but associated with low GC-content and low DNA methylation level. The base-transversion allele frequency is significantly low in coding-synonymous SNPs (P < 10). Another finding is that at the -1 and +1 positions relative to the somatic mutation sites, the SNP frequency was significantly higher (P < 3.2 × 10). Conclusions: The results suggested chromatin structure is different around coding SNPs and non-coding SNPs. New mutations tend to occur at the -1 and +1 position immediately near the SNPs.




Liu, H., Zhai, J., Luo, K., & Liu, L. (2014). Chromatin structure is distinct between coding and non-coding single nucleotide polymorphisms. BMC Molecular Biology, 15(1).

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