Tissue-specific usage of transposable element-derived promoters in mouse development

Abstract

Background Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. Results We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. 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. 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. Conclusion 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.

Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis

“…A small number of MER52A copies were lowly methylated in normal breast myoepithelial cells, liver, and pancreas tissues, suggesting that some MER52A copies maintain an active epigenetic state and may provide regulatory functions in normal cells. Finally, we found that several TEs overlapping hypoDMRs in GBM encompassed H3K4me3 signal, a mark of active promoters, in the GBM cell line U87, consistent with previous findings of hypomethylated TEs providing cryptic promoters during tumorigenesis 60 and embryonic development 61 (Fig. 7d ).…”

Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain

“…A wide range of oncogene-encoding TE-driven TcGTs have been documented in recent surveys of cancer databases (Jang et al 2019;Attig et al 2019), but the role of these transcript variants in physiological conditions remains largely undefined. Tissue-specific TcGTs have also been detected in the mouse developing intestine, liver, lung, stomach and kidney (Miao et al 2020). Here, we demonstrate not only the spatially and temporally orchestrated expression of TcGTs in the developing human brain, but also that these TcGTs are largely organ-and cell type-specific.…”

A species-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for preimplantation development

“…Yet the more prevalent retrotransposon exaptation is providing cis-regulatory elements that reprogram host gene expression in various developmental and pathological processes ( 14 – 22 ). Originating from ancient, exogenous retroviruses that no longer mobilize, a subset remain largely intact with LTR elements still harboring functional proviral sequences with intrinsic promoter activity, enhancer activity and splicing donor/acceptor sequences ( 16, 23 – 29 ), which substantially expand host gene regulatory landscape and transcript diversity. Due to their unique evolutionary history, retrotransposon mediated gene regulation is often species-specific( 25 ), and its functional importance in vivo remains largely unclear.…”