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Nat Chem. 2018 Jun;10(6):631-637. doi: 10.1038/s41557-018-0046-3. Epub 2018 Apr 23.

I-motif DNA structures are formed in the nuclei of human cells.

Author information

1
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
2
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, New South Wales, Australia.
3
Children's Medical Research Institute, University of Sydney, Westmead, Sydney, New South Wales, Australia.
4
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. m.dinger@garvan.org.au.
5
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, New South Wales, Australia. m.dinger@garvan.org.au.
6
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. d.christ@garvan.org.au.
7
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, New South Wales, Australia. d.christ@garvan.org.au.

Abstract

Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.

PMID:
29686376
DOI:
10.1038/s41557-018-0046-3

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