First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines

Abstract

Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced.In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.not peer-reviewed)

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

“…However, the majority of ChIP-exo peaks (69% − 605 out of 875) could not be enriched at the expected target ITRs of the Hsmar1 transposons, which are considered as natural landing sites for SETMAR chromosome binding. Significant off-target binding have been reported in another (unpublished) study [18] , but the reason for SETMAR’s non-ITR binding remained unexplained. We therefore decided to map the genomic landscape of SETMAR in a near-haploid human leukemia cell line (HAP1) to identify on-target and off-target binding sites at high resolution and to elucidate their role in terms of gene expression.…”