Figure 2.

Mechanisms of gene regulation by tumor-suppressor large ncRNAs. (A) lincRNA-p21 expression is directly induced by p53. Then, lincRNA-p21 specifically interacts with hnRNP-K for localization to gene promoters for repression. (B) GAS5 mimics the conformation of DNA GREs, binding to GR. In this manner, GR loses the ability to activate transcription of target genes. (C) DNA damage induces the expression of ncRNA CCND1 from the 5′ of cyclin D1/CCND1 gene. ncRNA CCND1 interacts with the TLS protein, inducing a conformational change in TLS that allows its binding to the cyclin D1 promoter. This causes inhibition of cyclin D1 gene expression by blocking of CBP and p300 HAT activity.