Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome

Throughout evolution, DNA transposons provide a recurrent supply of genetic information to give rise novel gene functions by fusion their transposase domain various domains host-encoded proteins. One these “domesticated”, transposase-derived factors is SETMAR/Metnase which naturally occurring protein that consists histone-lysine methyltransferase and an HsMar1 transposase. To elucidate the biological role SETMAR, it crucial identify genomic targets SETMAR specifically binds link sites regulation expression. Herein, we mapped landscape binding in near-haploid human leukemia cell line (HAP1) order on-target off-target at high resolution terms Our analysis revealed perfect correlation between inverted terminal repeats (ITRs) transposon remnants, are considered as natural target for binding. However, did not detect any untargeted events non-ITR sequences, calling into question previously proposed sites. We identified sequence fidelity ITR motif key factor determining affinity chromosomes, higher conservation sequences resulted increased chromatin stronger repression SETMAR-bound loci. These associations highlight how SETMAR’s fine-tune regulatory networks tumour cells.