Recurrent evolution of vertebrate transcription factors via transposase capture
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ABSTRACT:
PROVIDER: PRJNA625721 | ENA |
REPOSITORIES: ENA
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Project description:Recurrent evolution of vertebrate transcription factors via transposase capture [ChIP-Seq]
| PRJNA625725 | ENA
Project description:Recurrent evolution of vertebrate transcription factors via transposase capture [PRO-Seq]
| PRJNA625724 | ENA
Project description:How novel genes and cellular functions evolve is a central question in biology. Exon shuffling represents a potent mechanism to assemble new protein architectures. Here we show that DNA transposons, which are mobile and pervasive in genomes, have provided a recurrent supply of both exons and splice sites to assemble novel protein-coding genes in vertebrates. We find that transposase domains have been captured, primarily via alternative splicing, to form new fusion proteins at least 99 times independently over ~350 million years of tetrapod evolution. Evolution favors fusion of transposase DNA-binding domains to host regulatory domains, especially the Krüppel-associated Box (KRAB), suggesting transposase capture frequently yields new transcriptional repressors. Consistent with this model, we show that four KRAB-transposase fusion proteins born independently in different mammalian lineages repress gene expression in a sequence-specific fashion. Genetic knockout and rescue of the bat-specific KRABINER fusion protein in cell culture demonstrates that it binds its cognate transposons genome wide and controls a network of genes and cis-regulatory elements. Transposase capture is thus a powerful mechanism whereby transcription factors and their associated cis-regulatory networks can evolve by repurposing DNA transposon families, which provide both DNA binding domains and pre-existing genomic binding sites.
2020-05-08 | GSE148787 | GEO
Project description:How novel genes and cellular functions evolve is a central question in biology. Exon shuffling represents a potent mechanism to assemble new protein architectures. Here we show that DNA transposons, which are mobile and pervasive in genomes, have provided a recurrent supply of both exons and splice sites to assemble novel protein-coding genes in vertebrates. We find that transposase domains have been captured, primarily via alternative splicing, to form new fusion proteins at least 99 times independently over ~350 million years of tetrapod evolution. Evolution favors fusion of transposase DNA-binding domains to host regulatory domains, especially the Krüppel-associated Box (KRAB), suggesting transposase capture frequently yields new transcriptional repressors. Consistent with this model, we show that four KRAB-transposase fusion proteins born independently in different mammalian lineages repress gene expression in a sequence-specific fashion. Genetic knockout and rescue of the bat-specific KRABINER fusion protein in cell culture demonstrates that it binds its cognate transposons genome wide and controls a network of genes and cis-regulatory elements. Transposase capture is thus a powerful mechanism whereby transcription factors and their associated cis-regulatory networks can evolve by repurposing DNA transposon families, which provide both DNA binding domains and pre-existing genomic binding sites.
2020-05-08 | GSE148788 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-08 | GSE148789 | GEO
Project description:Genes with novel cellular functions may evolve through exon shuffling, which can assemble novel protein architectures. Here, we show that DNA transposons provide a recurrent supply of materials to assemble protein-coding genes through exon shuffling. We find that transposase domains have been captured-primarily via alternative splicing-to form fusion proteins at least 94 times independently over the course of ~350 million years of tetrapod evolution. We find an excess of transposase DNA binding domains fused to host regulatory domains, especially the Krüppel-associated box (KRAB) domain, and identify four independently evolved KRAB-transposase fusion proteins repressing gene expression in a sequence-specific fashion. The bat-specific KRABINER fusion protein binds its cognate transposons genome-wide and controls a network of genes and cis-regulatory elements. These results illustrate how a transcription factor and its binding sites can emerge.
| S-EPMC8186458 | biostudies-literature
Project description:The effect of overexpression of the At3g42170 hAT-like transposase on plant gene expression
2005-03-10 | E-MEXP-279 | biostudies-arrayexpress
Project description:Evolution of CpH methylation in vertebrate brains
| PRJNA594208 | ENA
Project description:Genomic rearrangements are a hallmark of childhood cancers, but the mutational processes underlying most of these variants remain unknown. We identified piggyBac transposable element derived 5 (PGBD5) as a highly expressed, enzymatically active domesticated human DNA transposase in a large subset of pediatric solid tumors, including rhabdoid tumors. Ectopic expression of PGBD5 in primary human cells was sufficient to induce fully penetrant cell transformation both in vitro and in immunodeficient mice in vivo. This activity required specific catalytic aspartic acid residues in the PGBD5 transposase domain as well as cellular non-homologous end-joining DNA repair, and was associated with distinct structural rearrangements defined by specific DNA sequence motifs. Similar genomic alterations, some recurrent, were found in primary human rhabdoid tumors. Thus, PGBD5 represents a new class of developmental oncogenic mutators in childhood solid tumors.
2016-12-05 | GSE81160 | GEO
Project description:Adaptive immunity and the five vertebrate NF-kB/Rel family members first appeared in cartilaginous fish, suggesting that NF-kB family expansion allowed the acquisition of new functions to regulate adaptive immune responses. Transcriptome profiling revealed that, even in macrophages, the NF-kB family member, c-Rel, most potently regulates a cytokine gene linked to adaptive immunity, Il12b, with limiting roles at key regulators of innate immunity. Neofunctionalization of c-Rel to regulate Il12b depends on its unique DNA-binding properties, which we examined using structural, biochemical, functional, and genomic approaches. Among our findings was functional c-Rel homodimer binding to motifs with little resemblance to canonical NF-kB motifs. To determine whether c-Rel’s unique binding properties drove c-Rel-RelA divergence, we compared binding properties in various vertebrate species. c-Rel-RelA binding properties diverged in mammals and amphibians but were comparable in earlier vertebrates, suggesting that divergent DNA binding emerged relatively late during vertebrate evolution to support increasing complexity of adaptive immune regulation.
2023-11-29 | GSE243010 | GEO