Long non-protein-coding RNAs (lncRNAs) act at different levels to regulate protein coding gene expression. lncRNAs can inhibit general protein-coding (pc) gene expression in trans (a) by preventing transcription factor (TF) activity (7SK lncRNA) or (b) by inhibiting RNAPII binding to DNA (B2 lncRNA). Xist lncRNA is transcribed from the X inactivation center (XIC) and inactivates a whole chromosome in cis (c) by recruiting epigenetic modifiers (EM). lncRNAs can regulate specific genes, acting in trans like HOTAIR (d) or in cis like HOTTIP (e) by directly recruiting epigenetic modifiers to certain genomic loci. In both cases the lncRNA binds EMs via a specific sequence or structure and targets them to promoter regions via DNA/RNA interaction elements to affect expression of the respective pc gene. Transcription of a lncRNA through a pc gene promoter or a cis-regulatory element (RE) affects pc gene expression in cis independent of the lncRNA product (f) by mechanisms discussed in the text. Both DNA strands are shown as separate boxes to indicate lncRNA transcription over the pc gene promoter in the antisense orientation. For details see text.