Transposons continue to mobilize within the human genome, sometimes forming hybrid sequences referred to as composite transposons. Some of these elements, such as SINE-VNTR-Alu (SVA) elements, have been associated with a variety of chromatin states. However, their precise regulatory activity remains poorly characterized. To fill this gap, Zhou et al. performed a genome-wide analysis and identified SVAs that harbor a bivalent chromatin state (H3K9me3 and H3K27ac) with variable levels of transcription. Combining a transposon reporter construct with a genome-wide CRISPR screen in K562 cells, the authors found the chromatin regulators of SVAs, which activate or suppress their transcription, two of which were validated via acute depletion. At the functional level, these elements are required for controlled distal gene expression, resembling enhancer-like activity. Finally, the authors explored the relevance of SVA bivalency during erythropoiesis and myelopoiesis, hinting at a role of these elements during the maturation and aging of these lineages. Further studies should strive to investigate the role of bivalent composite transposons in other transposon families and cell lineages.
Original reference: Cell https://doi.org/10.1016/j.cell.2025.07.014 (2025)