Modulation of Nrf2 expression by targeting i-motif DNA.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of cell detoxification, which maintains homoeostasis in healthy cells and promotes chemoresistance in cancer cells. Controlling the expression of this transcription factor is therefore of great interest. There are many compounds that have been shown to induce Nrf2 expression, but ligands that can inhibit Nrf2 are scant.

Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.

The insulin-linked polymorphic region is a variable number of tandem repeats region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of tandem repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression.

iM-Seeker: a webserver for DNA i-motifs prediction and scoring via automated machine learning.

DNA, beyond its canonical B-form double helix, adopts various alternative conformations, among which the i-motif, emerging in cytosine-rich sequences under acidic conditions, holds significant biological implications in transcription modulation and telomere biology. Despite recognizing the crucial role of i-motifs, predictive software for i-motif forming sequences has been limited. Addressing this gap, we introduce 'iM-Seeker', an innovative computational platform designed for the prediction and evaluation of i-motifs.

Utility of intercalator displacement assays for screening of ligands for i-motif DNA structures.

Cytosine rich sequences can form intercalated, i-motif DNA structures stabilized by hemi-protonated cytosine:cytosine base pairing. These sequences are often located in regulatory regions of genes such as promoters. Ligands targeting i-motif structures may provide potential leads for treatments for genetic disease.