What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

Abstract

Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis‐elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.

Transposable elements teach T cells new tricks

“…Indeed, a large body of evidence indicates that many essential processes in embryonic and placenta development are regulated by TE-derived proteins, promoters, noncoding RNAs, regulatory elements, and topologically associated domain boundary elements (reviewed in ref. 15). These findings have been described in both humans and mice, which have largely distinct TE profiles, implying that TEs may have an evolutionarily widespread role in shaping regulatory networks underlying early development.…”

Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

“…The expression profile of Zscan4c mRNA as defined in [ 39 ] is also displayed ( Figure 3 , and Table S1 ( Supplementary Materials ) for raw data). Of note, L1 elements also exert co-opted roles in totipotency and early developmental transitions [ 6 , 40 , 41 ]. Overexpression of the human DUX orthologue, DUX4 in human ESCs leads to an induction of ERVL promoters [ 35 ], which are usually expressed at the cleavage stage of human development [ 42 ].…”

“…On the other hand transposable elements (TEs) constitute an estimated two thirds of the human genome [ 2 , 3 ], and contribute to the regulation of protein-coding genes through their regulatory elements. TEs exercise a complex dialog with their host genomes that is distinct from a conventional virus-host arms race because they are not only potential parasites, but also a vital source of genome innovation [ 4 , 5 , 6 , 7 , 8 ]. TEs are subject to epigenetic silencing by histone modifications and DNA methylation [ 9 , 10 , 11 ] and become mutated and inactive over the course of evolution.…”

Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

“…How enhancers arise and rewire the gene regulatory network in plants is unclear. Transposable Elements (TEs) of various superfamilies have been proposed as a source of new regulatory elements [15] and have been shown to be involved in the rewiring of gene regulatory networks for some key tissue-specific biological functions in animals [16]. In plants, examples of enhancers derived from a particular TE have been described [17,18,19], and a more general contribution of TEs to cis-regulatory elements has been highlighted in some species such as Capsella grandiflora [20] and maize, where at least a quarter of the thousands of putative enhancers were found to overlap TE annotations [8,10].…”