The human RNA-DNA interactome is cell type-specific and dynamic

In the past two decades, scientists have discovered that mammalian genomes are continuously transcribed, resulting in a plethora of RNA molecules with uncertain roles. Some of these RNA transcripts have been associated with transcriptional control and chromatin organization through their ability to interact with DNA, hinting at their crucial role in genome regulation.

Recent advancements in technology have allowed for the mapping of genome-wide RNA-DNA contacts; however, integrating these findings with other genomic data and across various cellular contexts remains a challenge. Within the FANTOM6 project, researchers have now produced RNA-DNA interaction maps in 16 distinct human cell types, subsequently merging these contacts with a multitude of other genomic data.

This comprehensive analysis reveals that the RNA-DNA interactome is both dynamic and cell-type specific, organized into intricate networks composed of diverse interactions that depend on factors such as distance, source type, and chromatin state of the interacting targets. The study identifies numerous regulatory elements whose activity fluctuates significantly when differentially bound by RNA transcripts, suggesting that thousands of RNA-DNA interactions could play a mechanistic role in gene expression.

This regulatory function is linked to RNA-protein interactions and is strongly associated with both cell type-specific traits and traits linked to diseases. Beyond offering valuable resources for future research in RNA-mediated chromatin regulation, cellular biology, and human diseases, this study establishes the RNA-DNA interactome as a novel genome regulatory layer that shapes and sustains cellular identity and behavior.