Work

The cellular landscape of i-motifs: genomic insights, methodological challenges, and the road ahead

Year: 2026

Type: article

Abstract: Non-canonical DNA structures add a dynamic layer of genome regulation beyond the classical double helix. I-motifs, cytosine-rich four-stranded DNA structures, are increasingly recognized as context-dependent regulators of genome function. Recent methodological advances, including i-motif-specific antibodies, in-cell NMR, and genome-wide profiling, have enabled their detection and functional interrogation. Here, we review progress in understanding i-motif formation, stability, and protein interactions, highlighting parallels and contrasts with G-quadruplex structures. We also discuss technical limitations, strategies for improving structure-specific resolution, and future opportunities to integrate biochemical, genomic, and imaging approaches to clarify the biological relevance and therapeutic potential of i-motifs.

Source: Genome biology

DOI: 10.1186/s13059-026-04044-8

Authors: Pallabi Sengupta, Nasim Sabouri

Institution: Umeå University

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,490

Funders: Wenner-Gren Stiftelserna, Cancerfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet