DNA methylation dynamics at transposable elements in mammals

2019 ◽  
Vol 63 (6) ◽  
pp. 677-689
Author(s):  
Natasha Jansz
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Transposable Element ◽  
Human Development ◽  
Developmental Regulation ◽  
Repetitive Sequences ◽  
Single Copy ◽  
Regulatory Sequences ◽  
Dynamic Regulation ◽  
Element Activity

Abstract Transposable elements dominate the mammalian genome, but their contribution to genetic and epigenetic regulation has been largely overlooked. This was in part due to technical limitations, which made the study of repetitive sequences at single copy resolution difficult. The advancement of next-generation sequencing assays in the last decade has greatly enhanced our understanding of transposable element function. In some instances, specific transposable elements are thought to have been co-opted into regulatory roles during both mouse and human development, while in disease such regulatory potential can contribute to malignancy. DNA methylation is arguably the best characterised regulator of transposable element activity. DNA methylation is associated with transposable element repression, and acts to limit their genotoxic potential. In specific developmental contexts, erasure of DNA methylation is associated with a burst of transposable element expression. Developmental regulation of DNA methylation enables transposon activation, ensuring their survival and propagation throughout the host genome, and also allows the host access to regulatory sequences encoded within the elements. Here I discuss DNA methylation at transposable elements, describing its function and dynamic regulation throughout murine and human development.

Structure and unusual characteristics of a new family of transposable elements in the sea urchin Strongylocentrotus purpuratus

1985 ◽  
Vol 5 (10) ◽  
pp. 2804-2813
Author(s):  
J B Cohen ◽  
B Hoffman-Liebermann ◽  
L Kedes
Keyword(s):  
Transposable Elements ◽  
Transposable Element ◽  
Sea Urchin ◽  
Strongylocentrotus Purpuratus ◽  
Repetitive Sequences ◽  
Inverted Repeats ◽  
Genomic Locus ◽  
Unusual Structure ◽  
New Family ◽  
Flanking Regions

The transposable element family TU of the sea urchin Strongylocentrotus purpuratus, a higher eucaryote, has recently been described (D. Liebermann, B. Hoffman-Liebermann, J. Weinthal, G. Childs, R. Maxson, A. Mauron, S.N. Cohen, and L. Kedes, Nature [London] 306:342-347, 1983). A member of this family, TU4, has an insertion, called ISTU4, of non-TU DNA. ISTU4 is a member of a family of repetitive sequences, which are present in some 1,000 copies per haploid S. purpuratus genome (B. Hoffman-Liebermann, D. Liebermann, L.H. Kedes, and S.N. Cohen, Mol. Cell. Biol. 5:991-1001, 1985). We analyzed this insertion to determine whether it is itself a transposable element. The nucleotide sequence of ISTU4 was determined and showed an unusual structure. There are four, approximately 150 nucleotides long, imperfect direct repeats followed by a single truncated version of these repeats. This region is bounded at either side by approximately 100-nucleotide-long sequences that are not related to each other or to the repeats. Nucleotide sequences at the boundaries of ISTU4-homologous and flanking regions in five genomic clones show that ISTU4 represents a family of sequences with discrete ends, which we call Tsp elements. We showed that the genomic locus that carries a Tsp element in one individual was empty in other individuals and conclude that Tsp elements are a new and different type of transposable element. Tsp elements lack two features common to most other transposable elements: Tsp integration does not result in the duplication of host DNA, and there are no inverted repeats at their termini, although short inverted repeats are present at a distance from the termini.

scholarly journals Structure and unusual characteristics of a new family of transposable elements in the sea urchin Strongylocentrotus purpuratus.

1985 ◽  
Vol 5 (10) ◽  
pp. 2804-2813 ◽  
Author(s):  
J B Cohen ◽  
B Hoffman-Liebermann ◽  
L Kedes
Keyword(s):  
Transposable Elements ◽  
Transposable Element ◽  
Sea Urchin ◽  
Strongylocentrotus Purpuratus ◽  
Repetitive Sequences ◽  
Inverted Repeats ◽  
Genomic Locus ◽  
Unusual Structure ◽  
New Family ◽  
Flanking Regions

The transposable element family TU of the sea urchin Strongylocentrotus purpuratus, a higher eucaryote, has recently been described (D. Liebermann, B. Hoffman-Liebermann, J. Weinthal, G. Childs, R. Maxson, A. Mauron, S.N. Cohen, and L. Kedes, Nature [London] 306:342-347, 1983). A member of this family, TU4, has an insertion, called ISTU4, of non-TU DNA. ISTU4 is a member of a family of repetitive sequences, which are present in some 1,000 copies per haploid S. purpuratus genome (B. Hoffman-Liebermann, D. Liebermann, L.H. Kedes, and S.N. Cohen, Mol. Cell. Biol. 5:991-1001, 1985). We analyzed this insertion to determine whether it is itself a transposable element. The nucleotide sequence of ISTU4 was determined and showed an unusual structure. There are four, approximately 150 nucleotides long, imperfect direct repeats followed by a single truncated version of these repeats. This region is bounded at either side by approximately 100-nucleotide-long sequences that are not related to each other or to the repeats. Nucleotide sequences at the boundaries of ISTU4-homologous and flanking regions in five genomic clones show that ISTU4 represents a family of sequences with discrete ends, which we call Tsp elements. We showed that the genomic locus that carries a Tsp element in one individual was empty in other individuals and conclude that Tsp elements are a new and different type of transposable element. Tsp elements lack two features common to most other transposable elements: Tsp integration does not result in the duplication of host DNA, and there are no inverted repeats at their termini, although short inverted repeats are present at a distance from the termini.

scholarly journals Tools and best practices for retrotransposon analysis using high-throughput sequencing data

Mobile DNA ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aurélie Teissandier ◽  
Nicolas Servant ◽  
Emmanuel Barillot ◽  
Deborah Bourc’his
Keyword(s):  
Transposable Elements ◽  
Transposable Element ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Reference Genome ◽  
Repetitive Sequences ◽  
Simulated Data ◽  
Sequencing Data ◽  
Sequencing Technologies ◽  
Human Genomes

Abstract Background Sequencing technologies give access to a precise picture of the molecular mechanisms acting upon genome regulation. One of the biggest technical challenges with sequencing data is to map millions of reads to a reference genome. This problem is exacerbated when dealing with repetitive sequences such as transposable elements that occupy half of the mammalian genome mass. Sequenced reads coming from these regions introduce ambiguities in the mapping step. Therefore, applying dedicated parameters and algorithms has to be taken into consideration when transposable elements regulation is investigated with sequencing datasets. Results Here, we used simulated reads on the mouse and human genomes to define the best parameters for aligning transposable element-derived reads on a reference genome. The efficiency of the most commonly used aligners was compared and we further evaluated how transposable element representation should be estimated using available methods. The mappability of the different transposon families in the mouse and the human genomes was calculated giving an overview into their evolution. Conclusions Based on simulated data, we provided recommendations on the alignment and the quantification steps to be performed when transposon expression or regulation is studied, and identified the limits in detecting specific young transposon families of the mouse and human genomes. These principles may help the community to adopt standard procedures and raise awareness of the difficulties encountered in the study of transposable elements.

scholarly journals Single-cell multi-omic profiling of chromatin conformation and DNA methylome

2018 ◽  
Author(s):  
Dong-Sung Lee ◽  
Chongyuan Luo ◽  
Jingtian Zhou ◽  
Sahaana Chandran ◽  
Angeline Rivkin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Cell Types ◽  
Mouse Cell ◽  
Regulatory Sequences ◽  
Chromatin Conformation ◽  
Cell Type ◽  
Dynamic Regulation ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractRecent advances in the development of single cell epigenomic assays have facilitated the analysis of gene regulatory landscapes in complex biological systems. Methods for detection of single-cell epigenomic variation such as DNA methylation sequencing and ATAC-seq hold tremendous promise for delineating distinct cell types and identifying their critical cis-regulatory sequences. Emerging evidence has shown that in addition to cis-regulatory sequences, dynamic regulation of 3D chromatin conformation is a critical mechanism for the modulation of gene expression during development and disease. It remains unclear whether single-cell Chromatin Conformation Capture (3C) or Hi-C profiles are suitable for cell type identification and allow the reconstruction of cell-type specific chromatin conformation maps. To address these challenges, we have developed a multi-omic method single-nucleus methyl-3C sequencing (sn-m3C-seq) to profile chromatin conformation and DNA methylation from the same cell. We have shown that bulk m3C-seq and sn-m3C-seq accurately capture chromatin organization information and robustly separate mouse cell types. We have developed a fluorescent-activated nuclei sorting strategy based on DNA content that eliminates nuclei multiplets caused by crosslinking. The sn-m3C-seq method allows high-resolution cell-type classification using two orthogonal types of epigenomic information and the reconstruction of cell-type specific chromatin conformation maps.

scholarly journals Indication of family-specific DNA methylation patterns in developing oysters

2014 ◽  
Author(s):  
Claire E. Olson ◽  
Steven B. Roberts
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Transposable Element ◽  
Crassostrea Gigas ◽  
Developmental Stages ◽  
Epigenetic Modification ◽  
Genomic Region ◽  
Future Research ◽  
Sib Families ◽  
Methylation Patterns

Background DNA methylation is an epigenetic modification that is ubiquitous across many eukaryotes, with variable patterns and functions across taxa. The roles of DNA methylation during invertebrate development remain enigmatic, especially regarding the inheritance and ontogenetic dynamics of methylation. In order to better understand to what degree DNA methylation patterns are heritable, variable between individuals, and changing during Crassostrea gigas development, we characterized the genome-wide methylome of Crassostrea gigas sperm and larvae from two full-sib families nested within a maternal half-sib family across developmental stages. Results Bisulfite treated DNA sequencing of Crassostrea gigas sperm and larvae at 72 hours post fertilization and 120 hours post fertilization revealed DNA methylation ranges from 15-18%. Our data suggest that DNA methylation patterns are inherited, as methylation patterns were more similar between the two sires and their offspring compared to methylations pattern differences among developmental stages. Loci differing between the two paternal full-sib families (189) were found throughout the genome but were concentrated in transposable elements. The proportion of differentially methylated loci among developmental stages was not significantly greater in any genomic region. Conclusions This study provides the first single-base pair resolution DNA methylomes for both oyster sperm and larval samples from multiple crosses. Assuming DNA methylation is introduced randomly, the predominance of differentially methylated loci between families within transposable elements could be associated with selection against altering methylation in gene bodies. For instance, differentially methylated loci in gene bodies could be lethal or deleterious, as they would alter gene expression. Another possibility is that differentially methylated loci may provide advantageous phenotypic variation by increasing transposable element mobility. Future research should focus on the relationship between epigenetic and genetic variation, and explore the possible relationship of DNA methylation and transposable element activity.

Detection of DNA Methylation Changes Surrounding Transposable Elements

BIO-PROTOCOL ◽  
2013 ◽  
Vol 3 (11) ◽  
Author(s):  
Beery Yaakov ◽  
Khalil Kashkush
Keyword(s):  
Dna Methylation ◽  
Transposable Elements

scholarly journals Androgenic-Induced Transposable Elements Dependent Sequence Variation in Barley

2021 ◽  
Vol 22 (13) ◽  
pp. 6783
Author(s):  
Renata Orłowska ◽  
Katarzyna A. Pachota ◽  
Wioletta M. Dynkowska ◽  
Agnieszka Niedziela ◽  
Piotr T. Bednarek
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Dna Sequence ◽  
Sequence Variation ◽  
Nuclear Dna ◽  
Point Mutations ◽  
Mobile Elements ◽  
Dna Demethylation ◽  
Plant Genome

A plant genome usually encompasses different families of transposable elements (TEs) that may constitute up to 85% of nuclear DNA. Under stressful conditions, some of them may activate, leading to sequence variation. In vitro plant regeneration may induce either phenotypic or genetic and epigenetic changes. While DNA methylation alternations might be related, i.e., to the Yang cycle problems, DNA pattern changes, especially DNA demethylation, may activate TEs that could result in point mutations in DNA sequence changes. Thus, TEs have the highest input into sequence variation (SV). A set of barley regenerants were derived via in vitro anther culture. High Performance Liquid Chromatography (RP-HPLC), used to study the global DNA methylation of donor plants and their regenerants, showed that the level of DNA methylation increased in regenerants by 1.45% compared to the donors. The Methyl-Sensitive Transposon Display (MSTD) based on methylation-sensitive Amplified Fragment Length Polymorphism (metAFLP) approach demonstrated that, depending on the selected elements belonging to the TEs family analyzed, varying levels of sequence variation were evaluated. DNA sequence contexts may have a different impact on SV generated by distinct mobile elements belonged to various TE families. Based on the presented study, some of the selected mobile elements contribute differently to TE-related SV. The surrounding context of the TEs DNA sequence is possibly important here, and the study explained some part of SV related to those contexts.

scholarly journals Arabidopsis MORC proteins function in the efficient establishment of RNA directed DNA methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Xue ◽  
Zhenhui Zhong ◽  
C. Jake Harris ◽  
Javier Gallego-Bartolomé ◽  
Ming Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Transposable Element ◽  
Zinc Finger ◽  
Protein Function ◽  
C Elegans ◽  
Eukaryotic Organisms

AbstractThe Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms.

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