Gene regulation by non-coding RNAs in the 3D genome architecture

Appropriate gene expression is essential for producing the correct amount of proteins at the right time, which is critical for living organisms. In the three-dimensional (3D) space of the nucleus, genomes are folded into higher order chromatin structures that are intimately associated with epigenetic factors, including histone modifications and nuclear long non-coding RNAs (lncRNAs). LncRNAs regulate transcription for both activation and repression, either in cis or in trans. Many ncRNAs are expressed in development-specific, differentiation-specific, and disease-specific manners, suggesting that they are critical regulators for organ generation and maintenance. In this review, we mainly describe the following ncRNAs: Xist, involved in X chromosome inactivation, Firre, which serves as a platform for trans-chromosomal associations, and UMLILO and ELEANORS, which co-regulate genes involved in the immune response and breast cancer, respectively. These ncRNAs are gene regulators in the context of the 3D genome structure.