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DNA-only Transposons02:57

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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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Enhancer activation from transposable elements in extrachromosomal DNA.

Katerina Kraft1, Sedona E Murphy2,3,4, Matthew G Jones1,5

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Biorxiv : the Preprint Server for Biology
|September 16, 2024
PubMed
Summary
This summary is machine-generated.

Extrachromosomal DNA (ecDNA) in colorectal cancer can activate normally silent repetitive elements, driving MYC oncogene amplification and tumor evolution. This reactivation on ecDNA offers new avenues for cancer diagnostics and therapies.

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Area of Science:

  • Cancer Biology
  • Genomics
  • Epigenetics

Background:

  • Extrachromosomal DNA (ecDNA) is prevalent in aggressive cancers, promoting oncogene amplification and tumor heterogeneity.
  • The nuclear organization and regulatory potential of ecDNA remain incompletely understood.

Purpose of the Study:

  • To investigate the nuclear architecture of MYC-amplified ecDNA in colorectal cancer.
  • To identify and characterize repetitive elements interacting with ecDNA and explore their regulatory roles.

Main Methods:

  • Utilized Hi-C, super-resolution imaging, and long-read sequencing to analyze ecDNA in colorectal cancer cells.
  • Focused on a specific LINE/L1 repetitive element co-amplified with MYC on ecDNA.

Main Results:

  • Observed frequent spatial proximity between ecDNA and 68 repetitive elements (ecDNA-interacting elements or EIEs).
  • A specific L1M4a1#LINE/L1 EIE, normally silenced, gained enhancer marks and was co-amplified with MYC on ecDNA.
  • This EIE enhanced MYC expression and was essential for cancer cell survival, acting as a structural variant upstream of MYC.

Conclusions:

  • Silent repetitive genomic elements can be reactivated and functionally co-opted on ecDNA.
  • Repeat element activation on ecDNA contributes to accelerated tumor evolution and heterogeneity.
  • These findings suggest potential diagnostic and therapeutic strategies targeting ecDNA-mediated repeat activation.