![]() Other studies also indicated the active roles of TEs in neurodegeneration and systemic lupus erythematosus. In particular, we reported highly active cryptic transcription of LTR12 subfamilies when the lung cancer cell line NCI-H1299 underwent treatment of a DNMT inhibitor and an HDAC inhibitor. We previously utilized the tissue-specific epigenetic landscape to detect the activation of TEs in human cancer cells. We further found that these tissue-specific activated TEs can be associated with tissue-specific transcription factors (TFs), suggesting that the TFs might directly control the activation of TEs in a tissue-specific manner. When TEs were unmethylated in a specific tissue, active enhancer histone modification marks, such as H3K4me1 and H3K27ac, were also enriched around these unmethylated TEs. In our previous study, we reported the tissue-specific pattern of DNA methylation of 928 TE subfamilies across different human tissues. Īctivation of silent TEs is tightly associated with epigenetic modification. Meanwhile, TEs were also found to play roles as promoters in early development and some terminally differentiated tissues. Recent evidence also suggests that TEs are significant contributors to the origin of vertebrate long non-coding RNAs. Specifically, TEs have been found to initiate some genes’ transcription, especially for genes involved in immunity or response to external stimuli. However, mounting evidence suggests that some TEs escape from epigenetic silencing and are actively involved in a diverse array of biological processes (e.g., embryogenesis and carcinogenesis) and can become an essential component (e.g., promoter, enhancer, or insulator) of gene regulatory networks in the host genome. In the mammalian genome, most TEs are believed to be epigenetically silenced in somatic cells. ![]() In order to resist the damaging effect of TEs, the host genome has evolved multiple mechanisms, in particular epigenetic repression, including DNA methylation and repressive histone methylation, to suppress the activity of TEs in the cell. Additionally, because of the highly abundant transcriptional factor binding sites in TE sequences, TEs also present a substantial regulatory potential to the host genome. Īs parasites in the mammalian genome, TEs can regulate their activities by hijacking the regulatory mechanism of the host genome. TEs generally belong to two main categories: DNA transposons, which mobilize themselves in the genome through a “cut and paste” mechanism and retrotransposons, which replicate themselves by a “copy and paste” mechanism and can reach to hundreds of thousand copies in the genome. TEs are highly repetitive DNA units and can reproduce themselves in the host genome. ![]() Within these non-coding sequences, approximately 37% of the mouse genome and 45% of the human genome are derived from different kinds of transposable elements (TEs), including LINE, SINE, ERV, and DNA transposons. In the mammalian genome, only about 2% of DNA can be translated into protein products the remaining ~ 98% of non-coding genome is considered to be “genomic dark matter” with unknown function. Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. We found that TEs are associated with over 20% of open chromatin regions during development. We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution.
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