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Additional file 8: of A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus

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posted on 2017-02-20, 05:00 authored by Dilip Kumar, Kia Puan, Anand Andiappan, Bernett Lee, Geertje Westerlaken, Doreen Haase, Rossella Melchiotti, Zhuang Li, Nurhashikin Yusof, Josephine Lum, Geraldine Koh, Shihui Foo, Joe Yeong, Alexessander Alves, Juha Pekkanen, Liang Sun, Astrid Irwanto, Benjamin Fairfax, Vivek Naranbhai, John Common, Mark Tang, Chin Chuang, Marjo-Riitta Jarvelin, Julian Knight, Xuejun Zhang, Fook Chew, Shyam Prabhakar, Liu Jianjun, De Yun Wang, Francesca Zolezzi, Michael Poidinger, E. Lane, Linde Meyaard, Olaf RĂśtzschke
Model on the potentiating effect of a regulatory CpG-SNP. A Conventional vs. regulatory CpG-SNPs. The methylation of CpG pairs results in the condensation of chromatin due to a tighter packaging of the histone-DNA complexes (open circle: non-methylated CpG, closed circle: methylated CpG). While a conventional CpG-SNP can assist this process by providing only one additional allele-dependent methylation site (middle panel), a regulatory CpG-SNP (such as rs612529) modulates the recruiting of CpG-modifying enzymes (right panel). In the case of rs612529, this seems to be mediated by the allele-specific binding of PU.1 to the T allele of the CpG-SNP. In monocytes PU.1 was reported to bind the demethylase Tet-2. B Potentiating effect. Recruitment of Tet-2 mediates the chromatin-opening by facilitating the demethylation of all CpG pairs in the vicinity. The epigenetic effect is allele-specific (T allele) and direction of the direction probably cell-type–dependent. (PDF 415 kb)

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