How a lncRNA Shapes Chromatin Structure to Control Gene Expression

Mammalian genomes encode many thousands of long non-coding RNAs (lncRNAs) that play important roles in diverse biological processes. As a class, lncRNAs are generally enriched in the nucleus and specifically within the chromatin-associated fraction. Here, we will discuss the evidence that many nuclear-retained lncRNAs can interact with various chromatin regulatory proteins and recruit them to specific sites on DNA to regulate gene expression and shape three-dimensional nuclear organization. Specifically, we will discuss emerging mechanistic insights derived from the Xist lncRNA, a paradigm for lncRNA-mediated gene regulation, into how lncRNAs regulate gene expression by localizing to genomic target sites, recruiting regulatory complexes, and reshaping nuclear organization.