SETMAR, a case of primate co-opted genes: towards new perspectives.

Background: We carry out a review of the history and biological activities of one domesticated gene in higher primates, SETMAR, by discussing current controversies. Our purpose is to open a new outlook that will serve as a framework for future work about SETMAR, possibly in the field of cognition development.

Main Body: What is newly important about SETMAR can be summarized as follows: (1) the whole protein sequence is under strong purifying pressure; (2) its role is to strengthen existing biological functions rather than to provide new ones; (3) it displays a tissue-specific pattern of expression, at least for the alternative-splicing it undergoes.

SETMAR Shorter Isoform: A New Prognostic Factor in Glioblastoma.

Recent evidence suggests that the chimeric protein SETMAR is a factor of interest in cancer, especially in glioblastoma. However, little is known about the expression of this protein in glioblastoma tissues, and no study has been done to assess if SETMAR could be a prognostic and/or diagnostic marker of glioblastoma. We analyzed protein extracts of 47 glioblastoma samples coming from a local and a national cohort of patients.

The epigenetic regulation of HsMar1, a human DNA transposon.

Background: Both classes of transposable elements (DNA and RNA) are tightly regulated at the transcriptional level leading to the inactivation of transposition via epigenetic mechanisms. Due to the high copies number of these elements, the hypothesis has emerged that their regulation can coordinate a regulatory network of genes. Herein, we investigated whether transposition regulation of HsMar1, a human DNA transposon, differs in presence or absence of endogenous HsMar1 copies.

SETMAR isoforms in glioblastoma: A matter of protein stability.

Glioblastomas (GBMs) are the most frequent and the most aggressive brain tumors, known for their chemo- and radio-resistance, making them often incurable. We also know that SETMAR is a protein involved in chromatin dynamics and genome plasticity, of which overexpression confers chemo- and radio-resistance to some tumors. The relationships between SETMAR and GBM have never been explored.

Kinetic analysis of the interaction of Mos1 transposase with its inverted terminal repeats reveals new insight into the protein-DNA complex assembly.

Transposases are specific DNA-binding proteins that promote the mobility of discrete DNA segments. We used a combination of physicochemical approaches to describe the association of MOS1 (an eukaryotic transposase) with its specific target DNA, an event corresponding to the first steps of the transposition cycle. Because the kinetic constants of the reaction are still unknown, we aimed to determine them by using quartz crystal microbalance on two sources of recombinant MOS1: one produced in insect cells and the other produced in bacteria.

Target capture during Mos1 transposition.

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step.

cAMP protein kinase phosphorylates the Mos1 transposase and regulates its activity: evidences from mass spectrometry and biochemical analyses.

Genomic plasticity mediated by transposable elements can have a dramatic impact on genome integrity. To minimize its genotoxic effects, it is tightly regulated either by intrinsic mechanisms (linked to the element itself) or by host-mediated mechanisms. Using mass spectrometry, we show here for the first time that MOS1, the transposase driving the mobility of the mariner Mos1 element, is phosphorylated.

Regulation of mariner transposition: the peculiar case of Mos1.

Background: Mariner elements represent the most successful family of autonomous DNA transposons, being present in various plant and animal genomes, including humans. The introduction and co-evolution of mariners within host genomes imply a strict regulation of the transposon activity. Biochemical data accumulated during the past decade have led to a convergent picture of the transposition cycle of mariner elements, suggesting that mariner transposition does not rely on host-specific factors.

Transposase-transposase interactions in MOS1 complexes: a biochemical approach.

Transposases are proteins that have assumed the mobility of class II transposable elements. In order to map the interfaces involved in transposase-transposase interactions, we have taken advantage of 12 transposase mutants that impair mariner transposase-transposase interactions taking place during transposition. Our data indicate that transposase-transposase interactions regulating Mos1 transposition are sophisticated and result from (i) active MOS1 dimerization through the first HTH of the N-terminal domain, which leads to inverted terminal repeat (ITR) binding; (ii) inactive dimerization carried by part of the C-terminal domain, which prevents ITR binding; and (iii) oligomerization.

In vitro recombination and inverted terminal repeat binding activities of the Mcmar1 transposase.

The Mcmar1 mariner element (MLE) presents some intriguing features with two large, perfectly conserved, 355 bp inverted terminal repeats (ITRs) containing two 28 bp direct repeats (DRs). The presence of a complete ORF in Mcmar1 makes it possible to explore the transposition of this unusual MLE. Mcmar1 transposase (MCMAR1) was purified, and in vitro transposition assays showed that it is able to promote ITR-dependent DNA cleavages and recombination events, which correspond to plasmid fusions and transpositions with imprecise ends.

Physical properties of DNA components affecting the transposition efficiency of the mariner Mos1 element.

Previous studies have shown that the transposase and the inverted terminal repeat (ITR) of the Mos1 mariner elements are suboptimal for transposition; and that hyperactive transposases and transposon with more efficient ITR configurations can be obtained by rational molecular engineering. In an attempt to determine the extent to which this element is suboptimal for transposition, we investigate here the impact of the three main DNA components on its transposition efficiency in bacteria and in vitro. We found that combinations of natural and synthetic ITRs obtained by systematic evolution of ligands by exponential enrichment did increase the transposition rate.

Site-directed integration of transgenes: transposons revisited using DNA-binding-domain technologies.

In the last 20 years, tools derived from DNA transposons have made major contributions to genetic studies from gene delivery to gene discovery. Various complementary and fairly ubiquitous DNA vehicles have been developed. Although many transposons are efficient DNA vehicles, they appear to have limited ability to target specific sequences, since all that is required at the integration locus is the presence of a short 2- to 4-bp sequence.

Mariner Mos1 transposase optimization by rational mutagenesis.

Mariner transposons are probably the most widespread transposable element family in animal genomes. To date, they are believed not to require species-specific host factors for transposition. Despite this, Mos1, one of the most-studied mariner elements (with Himar1), has been shown to be active in insects, but inactive in mammalian genomes.

First Mariner Mos1 transposase inhibitors.

We described chemical inhibitors of Mos1 transposition. Some were already known to affect a related prokaryotic transposase (Tn5) or HIV-1 integrase, whereas the other were new compounds in this field. The new compounds were all organized around a bis-(heteroaryl)maleimides scaffold.

Factors acting on Mos1 transposition efficiency.

Background: Mariner-like elements (MLEs) are widespread DNA transposons in animal genomes. Although in vitro transposition reactions require only the transposase, various factors depending on the host, the physico-chemical environment and the transposon sequence can interfere with the MLEs transposition in vivo.

Results: The transposition of Mos1, first isolated from drosophila mauritiana, depends of both the nucleic acid sequence of the DNA stuffer (in terms of GC content), and its length.

Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis.

Background: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions.

Assembly of the Tc1 and mariner transposition initiation complexes depends on the origins of their transposase DNA binding domains.

In this review, we focus on the assembly of DNA/protein complexes that trigger transposition in eukaryotic members of the IS630-Tc1-mariner (ITm) super-family, the Tc1- and mariner-like elements (TLEs and MLEs). Elements belonging to this super-family encode transposases with DNA binding domains of different origins, and recent data indicate that the chimerization of functional domains has been an important evolutionary aspect in the generation of new transposons within the ITm super-family. These data also reveal that the inverted terminal repeats (ITRs) at the ends of transposons contain three kinds of motif within their sequences.

Mariner Mos1 transposase dimerizes prior to ITR binding.

The mariner Mos1 synaptic complex consists of a tetramer of transposase molecules that bring together the two ends of the element. Such an assembly requires at least two kinds of protein-protein interfaces. The first is involved in "cis" dimerization, and consists of transposase molecules bound side-by-side on a single DNA molecule.

Conservation of Palindromic and Mirror Motifs within Inverted Terminal Repeats of mariner-like Elements.

The transposase of the mariner-like elements (MLEs) specifically binds as a dimer to the inverted terminal repeat of the transposon that encodes it. Two binding-motifs located within the inverted terminal sequences (ITR) are therefore recognized, as previously indicated, by biochemical data obtained with the Mos1 and Himar1 transposases. Here, we define the motifs that are involved in the binding of a MLE transposase to its ITR by analyzing the nucleic acid properties of the 5' and 3' ITR sequences from 45 MLEs, taking into account the fact that the transposase binds to the ITR, using its CRO binding domains and the general characteristics of the cro binding sites so far investigated.

Characterization of Mcmar1, a mariner-like element with large inverted terminal repeats (ITRs) from the phytoparasitic nematode Meloidogyne chitwoodi.

Two copies of a new mariner-like element (MLE) presenting unusual inverted terminal repeats (ITRs), Mcmar1-1 and Mcmar1-2, were cloned and sequenced in the genome of the phytoparasitic nematode Meloidogyne chitwoodi. Although the sequence features of these Mcmar1 transposons are commonplace and link them to the mariner family, at their extremities they have large 355-pb long inverted terminal repeats that are perfectly conserved. This characteristic distinguishes them from all the other MLEs so far described that have imperfectly conserved ITRs of about 26-30 bp.

The ITR binding domain of the Mariner Mos-1 transposase.

Mariner-like elements are widespread eukaryotic transposons, but Mos-1 is the only natural element that is known to be active. Little is known about the biochemistry of mariner transposition. The first step in the process is the binding of the transposase to the 5' and 3' inverted terminal repeats (ITRs) of the element.

The wild-type conformation of the Mos-1 inverted terminal repeats is suboptimal for transposition in bacteria.

The two inverted terminal repeats (ITRs) flanking the Mos-1 mariner element differ in sequence at four positions. Gel retardation experiments indicated that each of these differences has a significant impact on the quality of the interaction between the ITR and the Mos-1 transposase. We showed that the transposase binds to the 3' ITR better than to the 5' ITR.