Fig. 3: Gene regulatory activities of transposable elements.

TEs provide a rich source of cis-regulatory elements that are spread across the genome. When active or accessible, the gene regulatory potential of TEs is exploited by the host genome in many ways in normal and malignant haematopoiesis. (i) TEs can act as enhancers through the recruitment of TFs and interacting with nearby promoters, modulating expression. Where this is a proto-oncogene, TEs can contribute to the malignant phenotypes. (ii) TEs can also produce lncRNAs, where 83% of lncRNAs are reported to contain a TE. lncRNAs can have diverse functions from stabilising promoter-enhancer interactions to the recruitment of epigenetic modifiers to chromatin. (iii) TEs can also function as alternative promoters, leading to generation of chimeric transcripts, which may promote a pathogenic phenotype. (iv) Alternative splicing events can occur from the exonisation of TEs, where they may provide alternate splice donor and acceptor sites. These aberrantly spliced transcripts may impair normal protein function, result in mRNA degradation or be translated into neoantigens. (v) TEs are a reservoir for CTCF binding sites and other anchor proteins, thereby retaining the potential to form neo-TADs which can bring cis-regulatory sequences to non-target genes and modulate their expression. This can be in the form of enhancer-promoter interactions to increase gene expression, or the inverse insulator-promoter interactions that decrease gene expression. Created in BioRender.