News

10.02.2020

Junk is not always junk – about transposons and their role for totipotency

In the last years, the perception of repetitive, transposable elements, such as transposons or retrotransposons, has changed from ‘junk’ DNA to powerful regulators of gene expression. In an opinion article, Maria-Elena Torres-Padilla, Director of the Institute of Epigenetics and Stem Cells, summarizes and interprets the current understanding of the role of transposons in the regulation of mammalian totipotency.

Transposable DNA elements - remnants of viruses and other genomic elements - have accumulated in mammalian genomes during evolution and make up around the half of the genomic content. Generally, retrotransposons, which are the most abundant transposable elements in rodent and human genomes, are transcriptionally silent in most somatic cells implemented by constitutive heterochromatin signatures. However, in the mouse zygote and 2-cell stage embryo, such heterochromatin signatures are absent or atypical and until the blastocyst stage, many retrotransposons are actively transcribed. In the mouse model, only the zygote and each of the two blastomeres of the 2-cell stage embryo are truly totipotent meaning that they can give rise to a full organism by themselves. While it is still an enigma how the transcriptional dynamics of retrotransposons in totipotent cells are regulated, findings in 2-cell-like cells* (2CLCs) suggest a potential role for retrotransposons in changing cell fate and regulating the transcriptional program of the 2-cell-stage embryo. The discovery of 2CLC has shaped research of the past five years and has generated an enormous interest in characterizing 2CLCs and identifying regulators of their emergence. In the opinion article, M.-E. Torres-Padilla summarizes the current knowledge of the molecular features underlying 2CLC emergence including the role of MERVL** transposons for developmental programs and puts the findings in the context of cell fate changes and reprogramming of pluripotency to totipotency.

To read the full opinion article go here. The opinion article is part of the theme issue "Crossroads between transposons and gene regulation" based on the Royal Society discussion meeting held in May 2019 and explores how the way of thinking about transposons and their roles in a variety of species and biological contexts has changed with the genomics and gene editing revolutions. For all articles of the theme issue go here.

Further information:

* 2-cell-like cells are a subpopulation of cells and make up around 0.5% of a pluripotent mouse embryonic stem cells (ESCs) culture. They arise spontaneously or their emergence can be induced. 2-cell-like cells are an in vitro cell type that resembles the totipotent 2-cell stage embryo in many molecular characteristics, such as the transcriptional profile and chromatin accessibility.

** MERVL (Murine Endogenous RetroVirus with Leucine tRNA primer) transposons are DNA elements from a long terminal repeats (LTRs) family of endogenous retroviruses. Robust transcription of MERVL is one of the main features of 2-cell-like cells. Additionally, it has been shown that oocytes and early mouse embryos can use sequences of MERVL as alternative promoters for host genes. The human ERVL (HERVL) transposons are dissimilar in sequence to MERVL transposons. However, both have been shown to regulate zygotic genome activation.