The EMBO Workshop ‘The mobile genome: genetic and physiological impacts of transposable elements‘ took place in November at EMBL Heidelberg and virtually.

The 2025 edition assembled recognised experts from diverse disciplines, like genomics, epigenetics, structural biology, evolutionary biology, and developmental biology, as well as the next generation of scientists, to discuss the broad impact of TEs on organismal biology.

For this year’s edition of the meeting, we had 227 people attending on-site and 70 participants joining remotely. There were 7 fellowships provided by the EMBL Corporate Partnership Programme and EMBO. With the total of 140 posters to view, we held three poster sessions during which the presenters could discuss their research — their work was then voted for by all participants. There were three poster prizes awarded during the meeting. We are pleased to share with you all of the winners’ abstracts!

Using DiMeLo-seq to probe the epigenetic control of polymorphic transposable elements

Presenter: Caterina Francesconi

Authors: Caterina Francesconi, Angelos Katsikas, Fereshteh Dorazehi, Jacob Quiros, Vivien Horvath, Christopher Douse

Abstract:

Transposable elements (TEs), which constitute ~50% of the human genome, can alter gene expression both by acting as cis-regulatory elements and by modifying the chromatin environment. Due to their high disruptive potential if deregulated, they are subjected to several layers of control, often entangled. In particular, DNA methylation, histone modifications and transcriptional/post-transcriptional silencing mediated by complexes such as HUSH and KRAB-ZNF/TRIM28 are known to be involved in silencing TEs, in ways often specific to the developmental stage and TE subfamily. Probing the regulation and regulatory effects of young TE subfamilies is challenging, as the standard epigenetic profiling methods are based on short reads. The youngest LINE1 and SVA elements, present within the genome as multiple indistinguishable copies, are often unmappable. Additionally, polymorphic insertions, variable across individuals, and length polymorphisms, variable across cells and tissues as well as individuals, represent an additional hurdle. A recently developed molecular tool (DiMeLo-sequencing) allows epigenetic profiling through Oxford Nanopore long-read sequencing, circumventing the mappability challenges intrinsic to short-read approaches. Moreover, the tool outputs combined information on histone modifications and DNA methylation on an individual long-read level, with the potential of detangling the epigenetic regulation of polymorphisms. Here, we applied the DiMeLo-sequencing, targeting H3K4me3, to epigenetically profile the activation of young LINE1s and SVAs in different human stem cell lines lacking MORC2 and ZNF91, respectively, critical players in the silencing of those TE subfamilies. To validate the methodology, we compared the obtained histone methylation profile with those produced through cleavage under targets and release using nuclease, i.e. CUT&RUN, the golden standard of epigenetic profiling. We then focused on polymorphic TEs, leveraging the single long-read information provided by the DiMeLo-sequencing to assess the epigenetic control of these often-overlooked elements. Finally, we set to analyse the interplay between H3K4me3 and DNA methylation in the TE promoter region, assessing their correlation on a single locus resolution.

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Evolutionary drivers of transposable elements accumulation in swallowtail butterflies and passerine birds

Presenter: Alba Marino

Authors: Alba Marino, Pelle Scholten, Eliette Reboud, Bérénice Lafon, Marie-ka Tilak, Fabien Condamine, Annabelle Haudry, Anna-Sophie Fiston-Lavier, Benoit Nabholz

Abstract:

Genome size is a widely variable trait ranging seven orders of magnitude across the tree of life. While transposable elements (TEs) are known to be pivotal determinants of genome size, the evolutionary mechanisms underlying their proliferation or reduction in different lineages – and ultimately genome inflation or downsizing – are not well understood. TEs may disrupt genes, interfere with expression levels, induce chromosomal rearrangements, and increase the mutational risk: hence, they are considered as mostly neutral or deleterious to their host. In 2007, Michael Lynch postulated that the removal of selfish elements is as effective as the strength of selection, which is stronger in species with larger effective population sizes (Ne). Hence, larger genomes are expected in species with small Ne due to the random fixation of detrimental TEs (Mutational Hazard Hypothesis, MHH). Some empirical studies have found that genome size and TE content are associated with Ne variation, while others have not, leaving the question unresolved. Here, we study the impact of genetic drift on genome size variation and TE accumulation on short evolutionary times using two independent datasets with contrasted patterns of genome size or Ne, composed of 33 Papilionidae and 76 Passeriformes species. Indeed, comparisons across closely related species should reduce the variability of selective effects potentially intervening at broader phylogenetic scales. In Papilionidae, in spite of their 6-fold genome size variation, we fail to find an association between genetic drift indices (dN/dS, heterozygosity) and genome size, overall or recently accumulated TE content. Interestingly, larger genomes present more frequent lateral transfers of TEs. While more homogeneous in genome size, Passeriformes exhibit multiple transitions from mainland to insular lifestyle, thus providing contrasted Ne. No link between relaxed selection and genome size is observed in birds either. However, species undergoing stronger drift accumulate more TEs, and notably display higher loads of full-length, young elements.Our findings are consistent with a nearly-neutral accumulation of TEs in the short term in birds, as predicted by the MHH. However, this does not seem a general trend shared across taxa, nor reflected on longer-term differences in genome size.

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Rat KRAB-ZNF genes evolving through tandem duplications: targets of endogenous RNAi in oocytes

Presenter: Adam Vobruba

Authors: Adam Vobruba, Radek Malík, Josef Pasulka, Zuzana Loubalová, Marcos Kulmann, Valeria Buccheri, Petr Svoboda

Abstract:

In the common ancestor of hamsters and mice, the RNA interference (RNAi) pathway was resurrected by the insertion of an MT retrotransposon long terminal repeat, which drives oocyte-specific expression of a truncated isoform of the RNase III enzyme Dicer. This isoform efficiently processes long double-stranded RNA and, consequently, activates RNAi. In mouse oocytes, RNAi regulates many genes and silences transposable elements (TE) and is essential for fertility. While RNAi in rat oocytes also regulates TEs, its role in gene repression is, in contrast to mice, limited and concerns different genes. The transcripts most targeted by RNAi in rat oocytes mainly belong to dozens of previously uncharacterized tandemly duplicated genes, which carry arrays of DNA-binding zinc finger (ZNF) domains along with an effector domain – typically a repressive Krüppel-associated box (KRAB) domain. Characterized proteins of the KRAB-ZNF family typically serve as transcription factors and TE repressors. To test whether the targeted transcripts encode bona fide functional proteins regulating gene expression, we have ectopically expressed three representatives of these RNAi targets in mammalian cell culture. We show that they encode stable proteins with nuclear localization. ChIP-seq and RNA-seq experiments would reveal their DNA-binding specificity and ability to regulate gene expression. We hypothesize that oocyte-specific RNAi-mediated suppression was adopted to silence newly evolving KRAB-ZNF genes in rats and may represent a case of toxin-antidote genetic conflict, wherein rapidly duplicating KRAB-ZNF genes represent a toxin and RNAi acts as an antidote, mitigating their potentially negative effects.

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Kindly sponsored by EMBO Press

The EMBO Workshop ‘The mobile genome: genetic and physiological impacts of transposable elements‘ took place from 4 – 7 November 2025 at EMBL Heidelberg and virtually.