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Epigenetic Reprogramming in Early Embryo Development
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
In eukaryotes, two main types of TEs have been described, retrotransposons and DNA transposons. DNA transposons or class II TEs move by a simple “cut and paste” mechanism: A DNA transposon sequence is removed from one genomic location and inserted in a new genomic site, using a specialized protein termed transposase (67). Its proportion in the human and mouse genome is lower than 5%, and no active DNA-transposons are present in these genomes at present. On the other hand, retrotransposons, or class I TEs, move by a “copy and paste” mechanism of mobilization that requires reverse transcription of an intermediate TEs RNA. In the human and mouse, more than 95% of TEs belong to this class (66) and represent more than 35% of the genome (68).
ChIP-seq analysis
Published in Altuna Akalin, Computational Genomics with R, 2020
Mapping is a procedure of trying to locate the exact genomic location which created each genomic fragment, each sequenced read. Several tools are available for mapping ChIP-seq data sets: Bowtie, Bowtie2, BWA (Langmead et al., 2009; Langmead and Salzberg, 2012 b; Li and Durbin, 2009 b), and all of them have comparable sensitivity and specificity (Ruffalo et al., 2011). Read length is the variable with the biggest effect on the mapping procedure. The longer the sequenced reads, the more uniquely can the read be assigned to a position on the genome. Reads which are assigned ambiguously to multiple locations in the genome are called multi-mapping reads. Such fragments are most often produced by repetitive genomic regions, such as retrotransposons, pseudogenes or paralogous genes (Li and Freudenberg, 2014). It is important to, a priori, decide whether such duplicated regions are of interest for the current experimental setup (i.e. whether we want to study transcription factor binding in olfactory receptors). If they are, then the multi-mapping reads should be included in the analysis. If they are not, they should be omitted. This is done during the mapping step, by limiting the number of locations to which a read can map. The methodology of working with multi-mapping reads differs according to the use case, and will not be considered in this chapter. For more information, please see the references (Chung et al., 2011).
The effects of transpositions of functional I retrotransposons depend on the conditions and dose of parental exposure
Published in International Journal of Radiation Biology, 2023
Leigh Brown and Moss obtained cytogenetic results indicating the activity of I elements in the absence of dysgenic conditions in natural populations of D. melanogaster (Leigh Brown and Moss 1987). The high instability level of retrotransposons was also found in several inbred and isogenic strains (Di Franco et al. 1992; Pasyukova and Nuzhdin 1993). In conditions of inbreeding, I retrotransposons not only destabilize the genome but also have a high polymorphic structure (Moschetti et al. 2010). The observed sterility and the frequency of DNA damage in germ cells of irradiated non-dysgenic variants (Cha[Cs] and JA [w1118]) indicate genome destabilization due to moderate radiation-induced I-retrotransposition. This confirms the results of the Italian researchers who found a relatively high activity of I retrotransposons under non-dysgenic conditions (Moschetti et al. 2010). The sensitivity of germ cells of dysgenic/non-dysgenic females to irradiation depends on the efficiency of repair processes which is not the same at different stages of oogenesis. The resistance of germ cells is believed to depend on the meiosis itself since it can control proliferation of cells with damaged DNA (Matulis and Handel 2006).
RNA A-to-I editing, environmental exposure, and human diseases
Published in Critical Reviews in Toxicology, 2021
Retrotransposons (or “jumping genes,” via RNA intermediates) comprise almost half of the human genome. They are the discrete sequences of DNA that can move from region to region across genomes under environmental stress. By affecting human genomic structures, transposable elements contribute to genomic evolution. Besides, they modify the risks for various diseases, including cancer, by generating chromosome mutations (insertion/deletion), genomic instability, and disorder in gene expression. Retrotransposons include the widely studied LINE-1 and Alu elements that are defined as short interspersed nuclear elements (SINEs) and common in the primate genome (Bazak et al. 2014). In Alu elements, intramolecular double strand RNA occurs in introns and 3′ untranslated region which are subject to RNA editing (Nishikura 2016). Recent advances in deep sequencing accelerate our understanding of how RNA editing is common in Alu double stranded RNAs. Now, we have substantial evidence from various studies that RNA editing sites are commonly available in Alu elements. Approximately 1.6 million RNA editing sites were demonstrated in Alu elements which are much higher than is anticipated (Bazak et al. 2014). In another human transcriptome study, the authors reported that A-to-I RNA editing was common in human mRNAs containing 14,500 sites and located in untranslated regions and introns (Athanasiadis et al. 2004; Levanon et al. 2004).
Extracellular vesicles mediate the horizontal transfer of an active LINE-1 retrotransposon
Published in Journal of Extracellular Vesicles, 2019
Yumi Kawamura, Anna Sanchez Calle, Yusuke Yamamoto, Taka-Aki Sato, Takahiro Ochiya
Long interspersed element-1 (LINE-1 or L1) retrotransposons are autonomous mobile elements that are able to create new genomic insertions by reverse transcription of an RNA intermediate. The human genome contains more than 500,000 L1 sequences, out of which 100 remain potentially mobile in any given individual [1]. A full-length L1 element consists of a 5ʹ and 3ʹ UTR, two open reading frames (ORFs), and a poly-A tail. ORF1 encodes a 40 kDa protein with RNA biding and chaperone activities, and ORF2 encodes a 150 kDa protein that has endonuclease and reverse transcriptase activities [2]. Due to their propensity for intragenomic spread, they are ubiquitous in eukaryotic genomes and are considered to be a major force driving genomic variation [3–6]. L1 retrotransposons are capable of altering the genome by causing mutations, deletions and rearrangements, and their effects range from local genetic instability to large-scale genomic variation. In somatic cells, these elements are silenced by epigenetic and post-transcriptional mechanisms. However, active retrotransposition have been implicated in various diseases. More than 70 diseases have been documented to be associated with heritable and somatic retrotransposition events [4,7].