Pluto Bioinformatics

GSE84458: TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells [RNA-seq]

Bulk RNA sequencing

TET enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. We have performed a detailedinvestigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We foundthat TET1 and TET2 bind multiple TE classes that harbour a variety ofepigenetic signatures indicative of different functional roles.Namely, TETsco-bind with pluripotency factors to enhancer-like TEs that interact with highlyexpressed genes in ESCs, whose expression is partly maintained by the demethylating action of TET2. TETs and 5-hydroxymethylcytosine are also strongly enriched at the 5 UTR offull-length,evolutionarily young LINE1 elements, a pattern thatis conserved in human embryonic stem cells. TET depletion leads to a markedincrease in DNA methylation levels at LINE1s, but surprisingly their expression is stably maintained through additional TET-dependent activities. Specifically, we find that TET1 recruits the SIN3A co-repressive complex toLINE1s, ensuring their repression upon TET-driven hypomethylation. This dual nature of TET action may reflect the evolutionary battle between TEs and the host. Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. SOURCE: Miguel,R,Branco (m.branco@qmul.ac.uk) - Blizard Institute