Genome-wide mapping of SETMAR transposase binding sites in the human genome
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PROVIDER: PRJNA733352 | ENA |
REPOSITORIES: ENA
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Project description:SETMAR/Metnase is a naturally occurring fusion protein that consists of a histone-lysine methyltransferase domain and an HsMar1 transposase. To elucidate the biological role of SETMAR, it is crucial to identify genomic targets to which SETMAR specifically binds and link these sites to the regulation of gene expression. Herein, we mapped the genomic landscape of SETMAR in a near-haploid human leukemia cell line (HAP1) in order to identify on-target and off-target binding sites at high resolution and to elucidate their role in terms of gene expression. Our analysis revealed a perfect correlation between SETMAR and inverted tandem repeats (ITRs) of HsMar1 transposon remnants, which are considered as natural target sites for SETMAR chromosome binding. However, we did not detect any untargeted events at non-ITR sequences, calling into question previously proposed off-target binding sites. We identified sequence fidelity of the ITR motif as a key factor for determining the binding affinity of SETMAR for chromosomes, as higher ITR fidelity resulted in increased affinity for chromatin and stronger repression of SETMAR-bound gene loci. These associations highlight how SETMAR’s chromatin binding fine-tune gene regulatory networks in human tumour cells.
2021-07-14 | GSE175725 | GEO
Project description: Not available
| S-EPMC8327481 | biostudies-literature
Project description:Approximately 50 million years ago, the Hsmar1 transposon entered the primate lineage giving rise to a new protein, a chimeric fusion of a SET domain and the Hsmar1 transposase. This protein, SETMAR or Metnase, is broadly expressed in human tissues and has been shown to retain its ancestral sequence-specific binding to Hsmar1 terminal inverted repeat (TIR) sequences found at the ends of the transposons. Despite the fact that there were estimated to be anywhere from 1500-7000 TIR sites within the human genome, the relevance of SETMAR-TIR interactions was unknown. Here, we report the crystal structure of the SETMAR DNA-binding domain (DBD) complexed with TIR DNA at 2.37 Å. The DBD structure includes two helix-turn-helix motifs (HTH1 and HTH2), which dimerize through HTH1, and confer sequence-specific recognition of the TIR through nucleobase-specific interactions with R371 in HTH1 and R417, H427, S428, and R432 in HTH2. The extent of genome-wide binding was determined by chromatin immunoprecipitation sequencing (ChIP-seq) analysis yielding a total of 7457 SETMAR bound sites. The effect of SETMAR on the transcriptome was assessed by RNA-seq analysis; among the 177 differentially regulated transcripts, a cluster of histones on chromosome 6 were found to be repressed. The dimeric SETMAR structure with each DBD bound to TIR DNA, the presence of eleven TIR sites within the histone gene cluster, and previously reported DNA looping activity are consistent with a direct regulatory mechanism in which SETMAR represses mRNA expression for specific genes through chromatin looping.
2022-02-20 | GSE103017 | GEO
Project description:Approximately 50 million years ago, the Hsmar1 transposon entered the primate lineage giving rise to a new protein, a chimeric fusion of a SET domain and the Hsmar1 transposase. This protein, SETMAR or Metnase, is broadly expressed in human tissues and has been shown to retain its ancestral sequence-specific binding to Hsmar1 terminal inverted repeat (TIR) sequences found at the ends of the transposons. Despite the fact that there were estimated to be anywhere from 1500-7000 TIR sites within the human genome, the relevance of SETMAR-TIR interactions was unknown. Here, we report the crystal structure of the SETMAR DNA-binding domain (DBD) complexed with TIR DNA at 2.37 Å. The DBD structure includes two helix-turn-helix motifs (HTH1 and HTH2), which dimerize through HTH1, and confer sequence-specific recognition of the TIR through nucleobase-specific interactions with R371 in HTH1 and R417, H427, S428, and R432 in HTH2. The extent of genome-wide binding was determined by chromatin immunoprecipitation sequencing (ChIP-seq) analysis yielding a total of 7457 SETMAR bound sites. The effect of SETMAR on the transcriptome was assessed by RNA-seq analysis; among the 177 differentially regulated transcripts, a cluster of histones on chromosome 6 were found to be repressed. The dimeric SETMAR structure with each DBD bound to TIR DNA, the presence of eleven TIR sites within the histone gene cluster, and previously reported DNA looping activity are consistent with a direct regulatory mechanism in which SETMAR represses mRNA expression for specific genes through chromatin looping.
2022-12-31 | GSE103076 | GEO
Project description:Diversity of genomic targets of SETMAR isoforms in two colorectal cell lines
| PRJEB19196 | ENA
Project description:Genome-wide mapping of DsbR-binding sites
| PRJNA645568 | ENA
Project description:The piggyBac transposon system is widely used for biotechnology and genome engineering and is the founding member of a large superfamily of piggyBac-like elements. We investigated the role in transpositon of the nonconserved N-terminus in the piggyBac transposase, including the impact of predicted casein kinase phosphorylation sites within it.
2023-03-11 | PXD037132 | Pride
Project description:Genome-wide mapping sites of Ulp2 chromatin binding
| PRJNA540826 | ENA
Project description:Transposons impart dynamism to the genomes they inhabit and their movements frequently rewire the control of nearby genes. Occasionally, their proteins are domesticated when they evolve a new function. SETMAR is a protein methylase with a sequence-specific DNA binding domain. It began to evolve about 50 million years ago when an Hsmar1 transposon integrated downstream of a SET-domain methylase gene. Here we show that the DNA-binding domain of the transposase targets the enzyme to transposon-end remnants and that this is capable of regulating gene expression, dependent on the methylase activity. When SETMAR was modestly overexpressed in human cells, almost 1500 genes changed expression by more than 2-fold (65% up- and 35% down-regulated). These genes were enriched for the KEGG Pathways in Cancer and include several transcription factors important for development and differentiation. Expression of a similar level of a methylase-deficient SETMAR changed the expression of many fewer genes, 77% of which were down-regulated with no significant enrichment of KEGG Pathways. Our data is consistent with a model in which SETMAR is part of an anthropoid primate-specific regulatory network centered on the subset of genes containing a transposon end.
2018-10-01 | GSE108773 | GEO
Project description:Transcriptomic profiling of WT and SETMAR KO HEK293T cells.
2022-08-08 | GSE181978 | GEO