Association between Triplex-Forming Sites of Cardiac Long Noncoding RNA and Chromatin Organization.

This study explored the relationship between 3D genome organization and RNA-DNA triplex-forming sites of long noncoding RNAs (lncRNAs), a group of RNAs that do not code for proteins but are important factors regulating different aspects of genome activity. The triplex-forming sites of anti-sense cardiac lncRNA derived from DBD-Capture-Seq were examined and compared to modular features of 3D genome organization called topologically associated domains (TADs) obtained from Hi-C data. It was found that triplex-forming sites are positioned non-randomly in TADs and their boundaries. The triplex sites showed a preference for TAD boundaries over internal regions of TADs. Computational prediction analysis indicated that CTCF, the key protein involved in TAD specification, may interact with , and their binding sites correlate with each other. Examining locations of repeat elements in the genome suggests that the ability of lncRNA to form triplex sites with many genomic locations may be achieved by the rapid expansion of different repeat elements. Some of the triplex-forming sites were found to be positioned in regions that undergo dynamic chromatin organization events such as loss/gain of TAD boundaries during cardiac differentiation. These observed associations suggest that lncRNA-DNA triplex formation may contribute to the specification of TADs in 3D genome organization.