Abstract
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression, particularly in the context of chromatin-mediated gene silencing. A growing body of evidence indicates that many lncRNAs function as molecular scaffolds, recruiting chromatin-modifying complexes to specific genomic loci to establish and maintain repressive epigenetic states. This article synthesizes current knowledge on the scaffolding roles of lncRNAs in recruiting polycomb repressive complexes (PRCs), histone methyltransferases, and other chromatin modifiers to silence target genes. We present a comprehensive literature review covering key lncRNAs such as Xist, HOTAIR, and MEG3, and discuss the structural features that enable scaffold function. Using a meta-analytical approach, we integrate data from biochemical, cellular, and genome-wide studies to quantify the prevalence and specificity of lncRNA–chromatin modifier interactions. Our results identify over 30 lncRNAs with validated scaffolding roles, and we characterize their binding domains, interacting proteins, and downstream chromatin marks. We further demonstrate that disruption of lncRNA scaffold function leads to widespread transcriptional de-repression and aberrant chromatin states. These findings underscore the fundamental importance of lncRNA scaffolds in epigenetic regulation and highlight their potential as therapeutic targets in diseases characterized by epigenetic dysregulation, including cancer and developmental disorders.
Keywords
long non-coding RNA, scaffold, chromatin modifier, gene silencing, polycomb repressive complex, epigenetics, Xist, HOTAIR