More than causing (epi)genomic instability: emerging physiological implications of transposable element modulation

Abstract

Transposable elements (TEs) initially attracted attention because they comprise a major portion of the genomic sequences in plants and animals. TEs may jump around the genome and disrupt both coding genes as well as regulatory sequences to cause disease. Host cells have therefore evolved various epigenetic and functional RNA-mediated mechanisms to mitigate the disruption of genomic integrity by TEs. TE associated sequences therefore acquire the tendencies of attracting various epigenetic modifiers to induce epigenetic alterations that may spread to the neighboring genes. In addition to posting threats for (epi)genome integrity, emerging evidence suggested the physiological importance of endogenous TEs either as cis-acting control elements for controlling gene regulation or as TE-containing functional transcripts that modulate the transcriptome of the host cells. Recent advances in long-reads sequence analysis technologies, bioinformatics and genetic editing tools have enabled the profiling, precise annotation and functional characterization of TEs despite their challenging repetitive nature. The importance of specific TEs in preimplantation embryonic development, germ cell differentiation and meiosis, cell fate determination and in driving species specific differences in mammals will be discussed.

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

“…Moreover, the relationship between TEs and epigenetic control is two-way, and if DNA hypomethylation is a cause of TE activation, the presence of TEs in a genomic region is also a cause of chromatin hypermethylation. Thus, epigenetic modification of TE regulatory sequences can impact the expression of neighboring genes [ 25 , 26 , 27 ].…”

Role of Transposable Elements in Genome Stability: Implications for Health and Disease

“…It has been suggested that the presence of TE sequences, even without the ability to transpose, can disrupt the integrity of the genome [ 40 ]. The insertion of TEs often attracts epigenetic modifiers that not only modify the transposon sequences but also impact surrounding regions.…”

“…Several studies have suggested that TEs are involved in critical physiological functions such as regulation of stem cell properties, epithelial to mesenchymal transition, inflammation, and many more biological functions [ 40 ]. Evidence also suggests that TEs in mammals have contributed to adaptive characteristics such as increased gene expression, gene replication, and stress tolerance [ 68 ].…”

“…Evidence also suggests that TEs in mammals have contributed to adaptive characteristics such as increased gene expression, gene replication, and stress tolerance [ 68 ]. Of note, some of the most important physiological contributions are from the TE-derived genes, which in turn participate in a variety of biological functions [ 40 ]. One such example is the Metnase/SETMAR gene, which is a fusion gene comprising histone H3 methylase gene and a transposase belonging to the mariner transposon family; it has been shown to function as a domesticated primate transposon playing critical roles in non-homologous end-joining of DNA repair and replication [ 69 ] and confers resistance to ionizing radiations [ 70 ].…”

“…Transposable elements are crucial components in tissue development and morphology [ 71 ] as well as impact in synaptic plasticity and cognition [ 72 ].Transposon element expression is associated with a cytokine response and induces recruitment and infiltration of immune cells in cancer and other inflammatory diseases. Based on their mechanistic functions, TEs in mammals are categorized into TE-containing functional RNAs and TE-containing cis-regulatory elements [ 40 ] ( Figure 2 ). In the former category, TE-derived microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) modulate function of protein-coding genes.…”