In the vast and intricate genomes of flowering plants, transposable elements (TEs)—sometimes known as “jumping genes”—comprise an astonishingly large fraction of the DNA landscape. Once dismissed as mere genomic parasites or "junk DNA," these mobile genetic elements have increasingly been recognized for their potential to modulate gene regulation and influence plant function in subtle yet profound ways. Despite their ubiquity, the repetitive nature of TEs has made them notoriously difficult to study, particularly at the level of individual sequences and their regulatory impact. Traditional short-read sequencing technologies have largely been inadequate for resolving these elements, preventing scientists from fully appreciating the evolutionary and functional roles TEs play within complex plant genomes.
A recent groundbreaking study by Bubb, Hamm, Tullius, and colleagues has pushed the envelope in our understanding of TE biology in maize—the world’s premier cereal crop—by applying an advanced technique called long-read chromatin fibre sequencing, or Fiber-seq. This innovative approach combines the power of long-read sequencing with chromatin accessibility and methylation profiling, enabling unprecedented resolution of regulatory landscapes along individual DNA molecules. In maize, whose genome is heavily laden with transposons, Fiber-seq has illuminated how accessible chromatin regions (ACRs) and CpG methylation patterns interweave to reveal the multifaceted regulatory potential embedded within young and old transposable elements alike.
One of the seminal discoveries from this work lies in the identification of stereotypical patterns of accessible chromatin at young TEs—regions that tend to exhibit clear signatures of gene regulatory activity. These ACRs undergo a gradual degeneration with evolutionary age, painting a picture of dynamic epigenetic remodeling across evolutionary timescales. As TEs age, their chromatin profiles morph, losing some accessibility while gaining biochemical modifications that may prevent aberrant activation. Intriguingly, the research highlights a novel plant-specific epigenetic feature characterized by the simultaneous presence of hypermethylated CpG sites and chromatin accessibility, a combination that challenges conventional wisdom about the repressive nature of DNA methylation.
This counterintuitive epigenetic signature—where high levels of CpG methylation coexist with a shift toward open chromatin structure—emerges as a hallmark of TE-derived enhancers in maize. These enhancers appear to be preferentially marked in this way, setting plant TEs apart from their animal counterparts and suggesting a sophisticated regulatory interplay that has evolved specifically within the plant kingdom. The identification of such a signature sheds new light on how TEs can transcend their origins as selfish elements to become integral components of plant gene regulatory networks.
Moreover, TEs equipped with these ACRs are not merely passive architectural features; they are co-opted by the host genome to act as gene promoters, driving gene expression in ways that may contribute to phenotypic diversity and adaptability. The study meticulously demonstrates instances where TE promoters facilitate gene amplification, effectively using the mobile DNA elements as vehicles for expanding gene copy number. This TE-mediated gene amplification mechanism hints at a deeper evolutionary relationship between transposons and gene innovation, one that may have played a critical role in shaping the maize genome and its remarkable plasticity.
Beyond enhancers and promoters, the authors unveil a pervasive and distinct epigenetic signature directing TEs to specific genomic loci. This signature encompasses hypo-methylation of 5-methylcytosine within CpG contexts (hypo-5mCpG) coupled with diffuse chromatin accessibility. Such an epigenomic landscape appears to direct the insertion or retention of TEs at particular sites, thereby influencing genome architecture and potentially targeting regions conducive to further TE activity or gene regulation. Fascinatingly, these targeted locations include the very loci that first brought Barbara McClintock’s landmark discovery of TEs to light, connecting modern high-resolution epigenomic techniques back to the foundational moments of genetic research.
The implications of fiber-level chromatin profiling in maize extend far beyond fundamental plant biology. As maize is a staple crop feeding millions worldwide, understanding the regulatory potential of its vast TE landscape may unlock new avenues for crop improvement. By elucidating how TEs function as cis-regulatory elements, breeders and biotechnologists might harness these sequences for controlled gene expression modulation, improving traits such as stress resistance, growth rate, and yield. This work thereby lays the groundwork for translational genomics efforts that could revolutionize sustainable agriculture.
Technically, the use of Fiber-seq represents a significant leap forward in epigenomic resolution compared to previous methodologies. Unlike conventional short-read sequencing that fragments DNA and loses context, Fiber-seq retains long continuous DNA molecules, preserving the native arrangement of chromatin accessibility and methylation marks. This granular perspective is essential for resolving repetitive elements such as TEs, which are otherwise indistinguishable within short fragments. The ability to simultaneously profile DNA methylation and chromatin openness on single molecules provides a wealth of information about regulatory potential, chromatin states, and epigenetic heterogeneity.
The comprehensive genome-wide maps produced by Fiber-seq reveal not only the diversity of TE-associated ACRs but also their interplay with nearby genes and the broader chromatin landscape. The finding that young TEs carry distinct epigenetic signatures before degenerative processes sets in aligns with hypotheses about TE-driven innovation early after insertion, with a subsequent gradual silencing phase. This dynamic underscores the complex life cycle of TEs in plant genomes, oscillating between activity and repression while contributing to regulatory novelty.
Interestingly, the authors’ revelation of a plant-specific epigenetic configuration where hyper-CpG methylation and chromatin accessibility coexist also invites a reevaluation of existing models of gene regulation. Traditionally, DNA methylation is viewed as a repressive mark that correlates with chromatin compaction and gene silencing. Here, the maize TE enhancers challenge this paradigm, suggesting that plants may have evolved unique epigenetic mechanisms allowing methylated DNA regions to remain accessible for transcription factor binding or enhancer function. Such findings open new questions regarding the molecular players and pathways facilitating this unusual chromatin state.
The study also delves into the evolutionary trajectory of TEs, empirically linking molecular age with epigenetic patterns. By tracing how ACRs and methylation signatures evolve over time, the authors provide evidence for an epigenomic "aging" process that influences TE contribution to regulatory networks. This nuanced understanding informs broader evolutionary biology debates surrounding the domestication and functional integration of mobile genetic elements.
The connection to McClintock’s pioneering research provides a poetic coda to the study. The loci identified possess the same epigenetic signatures that initially framed TEs as influential genomic nodes decades ago, illustrating the enduring relevance of TE dynamics in genetics. This underscores how advanced technologies like Fiber-seq are rejuvenating classical gene regulatory questions with modern precision and scale.
As the field moves forward, the integration of Fiber-seq data with other omics technologies will undoubtedly enrich our comprehension of TE biology. Combining chromatin fiber sequencing with transcriptomics, proteomics, and 3D genome architecture mapping could unravel how TEs coordinate regulatory cascades and respond to environmental stimuli. Moreover, extension of Fiber-seq applications to other complex crop genomes may catalyze a paradigm shift in plant epigenomics and genomic breeding.
In sum, this landmark research by Bubb and colleagues opens a compelling window into the regulatory lives of transposable elements in maize, showcasing the power of long-read chromatin fibre sequencing to untangle one of the most challenging features of plant genomes. The discovery of novel epigenetic signatures and their functional ramifications reshapes our understanding of plant genome regulation and evolution, promising exciting translational insights for agriculture and biology alike.
Subject of Research: The regulatory potential of transposable elements in maize, focusing on chromatin accessibility and CpG methylation patterns using long-read chromatin fibre sequencing.
Article Title: The regulatory potential of transposable elements in maize.
Article References:
Bubb, K.L., Hamm, M.O., Tullius, T.W. et al. The regulatory potential of transposable elements in maize. Nat. Plants (2025). https://doi.org/10.1038/s41477-025-02002-z
Image Credits: AI Generated
