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Related Concept Videos

Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

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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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Overview of Transposition and Recombination02:13

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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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DNA-only Transposons02:57

DNA-only Transposons

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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
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LTR Retrotransposons03:08

LTR Retrotransposons

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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.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
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piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

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PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
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Translesion DNA Polymerases02:10

Translesion DNA Polymerases

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
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Related Experiment Video

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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Dnmt1 has de novo activity targeted to transposable elements.

Chuck Haggerty1,2, Helene Kretzmer1, Christina Riemenschneider1,3

  • 1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.

Nature Structural & Molecular Biology
|June 18, 2021
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Summary

DNA methyltransferase 1 (Dnmt1) exhibits novel de novo methylation activity, particularly targeting retrotransposons. This dual function, alongside its maintenance role, is crucial for stable epigenetic repression during development.

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Area of Science:

  • Epigenetics and Gene Regulation
  • Molecular Biology
  • Developmental Biology

Background:

  • DNA methylation is essential for mammalian development, notably for silencing retrotransposons.
  • The methylation landscape relies on both maintenance (Dnmt1) and de novo DNA methyltransferases (DNMT3A, DNMT3B).

Purpose of the Study:

  • To investigate the potential de novo methylation activity of DNA methyltransferase 1 (Dnmt1).
  • To characterize the mechanisms and genomic targets of Dnmt1's de novo methylation activity.

Main Methods:

  • Utilized whole-genome bisulfite sequencing and long-read Nanopore sequencing.
  • Employed genetically engineered methylation-depleted mouse embryonic stem cells and knockout lines.
  • Performed molecular characterization to assess Dnmt1's activity and genomic recruitment.

Main Results:

  • Demonstrated that Dnmt1 possesses in vitro and in vivo de novo methylation activity.
  • Identified specific retrotransposons as targets for Dnmt1's de novo methylation.
  • Showed that Dnmt1's de novo activity is dependent on Uhrf1 and co-localizes with Uhrf1, Trim28, and H3K9me3 enrichment.

Conclusions:

  • Dnmt1 functions in both de novo and maintenance DNA methylation contexts.
  • This dual activity, especially at retrotransposons, enhances epigenetic stability and long-term repression.
  • The findings reveal a more versatile role for Dnmt1 in epigenetic regulation throughout development.