RNA-DNA triple helices consist of three strands: a DNA duplex bound by an RNA strand in the major groove. The RNA strand interacts via Hoogsteen base pairing, while the DNA duplex maintains Watson-Crick pairing. Hoogsteen base pairing involves unique hydrogen bonds, where purine bases (e.g., adenine or guanine) flip to a syn conformation, interacting with specific atoms on pyrimidines (e.g., thymine or cytosine) in the major groove (Figure 1A).
The DNA sequence consists of a polypurine strand, serving for the specific interaction and Hoogsteen base pairing with three different kinds of Triplex Forming Sequence (TFS) binding motifs. The TFS can be classified into Pyrimidine-, Purine-, and Mixed-motifs, consisting of TFS sequences with only pyrimidine, purine, or both types of nucleotides, respectively (Figure 1B). The sequence composition of the TFS directs the third strand’s 5′ to 3′ orientation relative to the TTS purine strand, the Pyrimidine-motif binds in parallel, the Purine-motif bind anti-parallel, and the Mixed-motif can bind inboth orientations.
RNA-DNA triple helices play a role in Gene Regulation and Chromatin Structure. Triplexes can regulate gene expression by forming at promoters or enhancers, influencing transcription factor binding and chromatin structure, altering chromatin accessibility and impacting gene expression during development and differentiation.
The triplex structures are sequence-specific and less stable than Watson-Crick pairings, but they are stabilized by the histone H3 tail of neighboring nucleosomes. We are studying the Triplex-Chromatin interaction and its application in the regulation of gene expression.
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