Schematic illustration of the potential mechanisms by which lncRNAs regulate chromatin structure and gene transcription. (A) Scaffold: lncRNA acts as a scaffold to orchestrate active or repressive chromatin (eg, PRC2 complex and H3K27me3 in Xi) over a large distance. (B) Recruitment/guide: lncRNA acts a mediator to recruit and guide the coactivator complex to enhancer/promoter for gene transcription. (C) Stabilization: lncRNAs produced in proximity of gene specifically associate with TFs or cofactors to facilitate gene transcription (upper panel). Depletion of lncRNA (dashed line) leads to degradation of TFs and cofactors, resulting in transcription silencing (lower panel). (D) Decoy: lncRNA acts as molecular decoy that dissociates promoter-bound TFs from the gene, leading to transcriptional inhibition. (E) Bridge: lncRNA or nearby enhancer-produced eRNA binds to and stabilizes the enhancer and promoter loop, leading to transcriptional activation. CoA, coactivator; Med, mediator.