FIGURE 2.

Known molecular mechanisms underlying cis-regulation by lncRNAs. (A) Recruitment of chromatin-modifying enzymes by cis-regulatory lncRNAs. Morrbid represses the Bcl2l11 gene by recruiting the PRC2 complex to the Bcl2l11 promoter (Kotzin et al., 2016). HOTTIP recruits the WDR5 subunit of the MLL complex, resulting in the deposition of the H3K4me3 mark and subsequent activation of the HOXA distal genes (Wang et al., 2011). (B) LncRNA prevents binding of an inhibitory protein to a promoter, which results in gene activation. Jpx lncRNA competes with DNA for the binding of CTCF on Xist promoter, and this enables activation of Xist expression (Sun et al., 2013). Transcription of ecCEBPA, a sense-overlapping lncRNA of the CEBPA gene, prevents the silencing of CEBPA by inhibiting DNMT1-dependent DNA methylation of CEBPA promoter (Di Ruscio et al., 2013). (C) Increased chromatin accessibility by DNA binding of lncRNA. The Khps1 lncRNA forms a triple helix with the promoter of SPHK1, which leads to the successive recruitment of p300/CBP and H3K27 acetylation of SPHK1 promoter, facilitating the binding of TFs on the SPHK1 promoter (Postepska-Igielska et al., 2015). VIM-AS lncRNA sustains the expression of the VIM gene by forming an R-loop at the VIM promoter (Boque-Sastre et al., 2015). The R-loop helps keeping the chromatin open, allowing TFs of the NF-kB pathway to bind to the VIM promoter and activate VIM expression.