Transposable elements (TEs) promote genetic innovation but also threaten genome stability. Despite multiple layers of host defence, TEs actively shape mammalian-specific developmental processes, particularly during pre-implantation and extra-embryonic development and at the maternal–fetal interface. Here, we review how TEs influence mammalian genomes both directly by providing the raw material for genetic change and indirectly via co-evolving TE-binding Kruppel-associated box zinc finger proteins (KRAB-ZFPs). Throughout mammalian evolution, individual activities of ancient TEs were co-opted to enable invasive placentation that characterizes live-born mammals. By contrast, the widespread activity of evolutionarily young TEs may reflect an ongoing co-evolution that continues to impact mammalian development. In this Review, Senft and Macfarlan discuss the diverse ways by which transposable elements (TEs) contribute to mammalian development and evolution, including direct contributions through TE-derived regulatory elements, RNAs and proteins, as well as indirect effects through the evolution of a TE repression system, the Kruppel-associated box zinc finger proteins (KRAB-ZFPs).

Transposable elements shape the evolution of mammalian development.

Abstract Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic datasets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser ( http://comparativegateway.wustl.edu ). It allows users to load functional genomic datasets/annotations mapped to different genomes and display them over syntenic regions simultaneously. The browser also displays genetic differences between the genomes from single nucleotide variants (SNVs) to structural variants (SVs) to visualize the association between epigenomic differences and genetic differences. Instead of anchoring all datasets to the reference genome coordinates, it creates independent coordinates of different genome assemblies to faithfully present features and data mapped to different genomes. It uses a simple, intuitive genome-align track to illustrate the syntenic relationship between different species. It extends the widely used WashU Epigenome Browser infrastructure and can be expanded to support multiple species. This new browser function will greatly facilitate comparative genomic/epigenomic research, as well as support the recent growing needs to directly compare and benchmark the T2T CHM13 assembly and other human genome assemblies. 

/pdf/comparing-genomic-and-epigenomic-features-across-species-10yjcry0.pdf

Comparing Genomic and Epigenomic Features across Species Using the WashU Comparative Epigenome Browser

Transposable elements (TEs) are genomic elements that are found in multiple copies in mammalian genomes. TEs were previously thought to have little functional relevance but recent studies have reported TE roles in multiple biological processes, particularly in embryonic development. To investigate the expression dynamics of TEs during human early development, we used long-read sequence data generated from in vitro differentiation of human pluripotent stem cells (hPSCs) to endoderm, mesoderm, and ectoderm lineages to construct lineage-specific transcriptome assemblies and accurately place TE sequences in their transcript context. Our analysis revealed that specific TE types, such as LINEs and LTRs, exhibit distinct expression patterns across different lineages. Notably, an expression outburst was observed in the ectoderm lineage, with multiple TE types showing dynamic expression trajectories. Additionally, certain LTRs, including HERVH and LTR7Y, were highly expressed in hPSCs and endodermal cells, but these HERVH and LTR7Y sequences originated from completely different transcripts. Interestingly, TE-containing transcripts exhibit distinct levels of transcript stability and subcellular localization across different lineages. Moreover, we showed a consistent trend of increased chromatin association of TE-containing transcripts in germ lineage cells compared to hPSCs. This study suggests that TEs contribute to human embryonic development through dynamic chromatin interaction. 

Transposable Element Expression and Sub-cellular Dynamics During hPSC Differentiation to Endoderm, Mesoderm, and Ectoderm Lineages

The human transcriptome contains many types of noncoding RNAs, which rival the number of protein-coding species. From long noncoding RNAs (lncRNAs) that are over 200 nucleotides long to piwi-interacting RNAs (piRNAs) of only 20 nucleotides, noncoding RNAs play important roles in regulating transcription, epigenetic modifications, translation, and cell signaling. Roles for noncoding RNAs in disease mechanisms are also being uncovered, and several species have been identified as potential drug targets. On May 11-14, 2021, the Keystone eSymposium "Noncoding RNAs: Biology and Applications" brought together researchers working in RNA biology, structure, and technologies to accelerate both the understanding of RNA basic biology and the translation of those findings into clinical applications.

Noncoding RNAs: biology and applications—a Keystone Symposia report

Retrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1{Delta}N isoform to promote cell proliferation. Cdk2ap1{Delta}N functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1{Delta}N, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1{Delta}N is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1{Delta}N expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence. One Sentence SummaryIn mammalian preimplantation embryos, retrotransposon promoters generate conserved gene isoforms, confer species-specific expression, and perform essential developmental functions.

https://www.biorxiv.org/content/biorxiv/early/2021/03/25/2021.03.24.436683.full.pdf

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

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