Similar Datasets
Project description:SETMAR regulates gene expression and alternative splicing
| PRJNA754125 | ENA
Project description:Born 45 million years ago, SETMAR is a fusion gene only present in higher primates. It is made of three exons, the two first given by the SET gene and coding for methyltransferase functions, the third given by the Hsmar1 transposase gene and coding for recombinase functions. The full length SETMAR protein (FL-SETMAR) is described as a genome keeper, expressed in main tissues, but with different levels. In cancer cells, the SETMAR gene is over-expressed, and FL-SETMAR sustains oncogenic processes, probably through its involvement in DNA repair by Non-Homologous End-Joining (NHEJ), replication stress response and chromosome decatenation. Under certain circumstances, SETMAR pre-mRNA undergoes alternative splicing, leading to the production of shorter proteins, enriched in cancer stem cells. One of them, S-SETMAR, was first discovered in glioblastoma (GB), and more recently in colorectal cancers. S-SETMAR lacks a part of the pre-SET domain and the whole SET domain, both encoded by exon 2. As a result, S-SETMAR is unable to methylate proteins, as does FL-SETMAR with a moderate efficiency. Little is known about the role of S-SETMAR. It has been recently shown that S-SETMAR, when enriched in tissues surrounding GB, correlates with an increased patient’s survival. In order to understand how S-SETMAR can have a protective role in glioblastoma biogenesis, the transcriptomes of established glioblastoma cell line expressing or not S-SETMAR were compared. This allowed the identification of deregulate pathways.
2025-10-10 | GSE255745 | GEO
Project description:SILAC labeled HT-1080 cell lysate (K0R0 and K8R10) were treated with active or catalytic inactive SETMAR methyltransferase enzyme. Samples were combined and proteins modified by methyl-lysine enriched by 3xMBT. Quantitative comparison identified candidate proteins with increase methylation following incubation with SETMAR.
2016-06-24 | PXD001635 | Pride
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: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:NONO-mediated alternative splicing of SETMAR inhibits lymphatic metastasis in bladder cancer
| PRJNA613734 | ENA
Project description:Bladder cancer patients with lymph node (LN) metastasis have an extremely poor prognosis and no effective treatment. The alternative splicing of precursor (pre-)mRNA participates in the progression of various tumors. However, the precise mechanisms of splicing factors and cancer-related variants in LN metastasis of bladder cancer remain largely unknown. The present study identified a splicing factor, non-POU domain-containing octamer-binding protein (NONO), that was significantly downregulated in bladder cancer tissues and correlated with LN metastasis status, tumor stage, and prognosis. Functionally, NONO markedly inhibited bladder cancer cell migration and invasion in vitro and LN metastasis in vivo. Mechanistically, NONO regulated the exon skipping of SETMAR by binding to its motif, mainly through the RRM2 domain. NONO directly interacted with splicing factor proline/glutamine rich (SFPQ) to regulate the splicing of SETMAR, and it induced metastasis suppression of bladder cancer cells. SETMAR-L overexpression significantly reversed the metastasis of NONO-knockdown bladder cancer cells, both in vitro and in vivo. The further analysis revealed that NONO-mediated SETMAR-L can induce H3K27me3 at the promotor of metastatic oncogenes and inhibit their transcription, ultimately resulting in metastasis suppression. Therefore, the present findings uncover the molecular mechanism of lymphatic metastasis in bladder cancer, which may provide novel clinical markers and therapeutic strategies for LN-metastatic bladder cancer.
| S-EPMC7791011 | biostudies-literature
Project description:RNA-seq in duplicates of a control cell line, TO, and three cell lines expressing full-length SETMAR, SM1, SM2 and SM3
2019-06-19 | GSE129870 | GEO
Project description:Mitochondrial translation was investigated by mitochondrial ribosome profiling (mitoRiboSeq) in three HEK293T cell lines: HEK293T wild-type (WT), TACO1 knockout (TACO1-KO), and TACO1 reconstituted (TACO1-KO + TACO1) cells
2025-01-29 | E-MTAB-14071 | biostudies-arrayexpress