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Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects

Author

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  • Xing Jian

    (Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health)

  • Gary Felsenfeld

    (Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health)

Abstract

Previous GWAS studies identified non-coding loci with parent-of-origin-specific effects on Type 2 diabetes susceptibility. Here we report the molecular basis for one such locus near the KRTAP5-6 gene on chromosome 11. We determine the pattern of long-range contacts between an enhancer in this locus and the human INS promoter 460 kb away, in the human pancreatic β-cell line, EndoC-βH1. 3C long range contact experiments distinguish contacts on the two sister chromosomes. Coupling with allele-specific SNPs allows construction of maps revealing marked differences in organization of the two sister chromosomes in the entire region between KRTAP5-6 and INS. Further mapping distinguishes maternal and paternal alleles. This reveals a domain of parent-of-origin-specific chromatin structure extending in the telomeric direction from the INS locus. This suggests more generally that imprinted loci may extend their influence over gene expression beyond those loci through long range chromatin structure, resulting in parent-of-origin-biased expression patterns over great distances.

Suggested Citation

  • Xing Jian & Gary Felsenfeld, 2021. "Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24635-2
    DOI: 10.1038/s41467-021-24635-2
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    References listed on IDEAS

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    1. Adam C. Bell & Gary Felsenfeld, 2000. "Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene," Nature, Nature, vol. 405(6785), pages 482-485, May.
    2. Ramya Raviram & Pedro P Rocha & Christian L Müller & Emily R Miraldi & Sana Badri & Yi Fu & Emily Swanzey & Charlotte Proudhon & Valentina Snetkova & Richard Bonneau & Jane A Skok, 2016. "4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments," PLOS Computational Biology, Public Library of Science, vol. 12(3), pages 1-23, March.
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