Brassica juncea is an allotetraploid, meaning its genome is the fused product of two diploid progenitor species. Its cells therefore contain an A-derived subgenome, denoted Aj, and a B-derived subgenome, denoted Bj, each of which carries many genes that originally came from a common ancestor. In a paper published in BMC Plant Biology, Shici Zhu, Guoqing Li and Jianbo Wang of Wuhan University and Guizhou Normal University set out to answer a deceptively simple question: why does one subgenome in this crop express its genes more strongly than the other? The relationship between epigenetic modifications, transposable elements and subgenome expression dominance had remained poorly understood in B. juncea, and the team assembled genome-wide maps of gene expression, DNA methylation and four histone marks to close that gap.

The first and most fundamental finding was a clear confirmation of expression asymmetry. Across the transcriptome, the Aj subgenome emerged as the dominantly expressed partner, producing higher levels of transcripts than the Bj subgenome under the conditions examined. This in itself echoes patterns reported in other allopolyploids, but the real contribution of the study lies in what follows: the researchers traced that expression imbalance back to systematic differences in the chemical decoration of the two sets of chromosomes and to starkly uneven distributions of transposable elements between them.

To read the epigenetic landscape, the team used whole-genome bisulfite sequencing, a technique that converts unmethylated cytosines to another base and thereby reveals the position of DNA methylation marks across the entire genome at single-nucleotide resolution. They layered on top of this chromatin immunoprecipitation sequencing, or ChIP-seq, for four histone modifications with well-characterized roles in gene regulation: H3K4me3, typically associated with active gene bodies; H3K27ac, an acetylation mark linked to active promoters and enhancers; H3K27me3, a repressive mark laid down by the Polycomb system; and H3K9me3, a hallmark of heterochromatin that silences repetitive DNA. Comparing these maps between the Aj and Bj subgenomes exposed a pronounced asymmetry, with the two subgenomes differing systematically in where and how heavily their DNA carries methyl groups and in the density of the silencing marks that decorate their chromatin.

The most striking epigenetic pattern involved DNA methylation and the repressive H3K9me3 modification. Both were biased toward the Bj subgenome, the very subgenome whose genes are expressed at lower levels. Methylation of cytosines in and around genes is well known to interfere with transcription factor binding and to recruit proteins that compact chromatin, and H3K9me3 plays a complementary role by anchoring heterochromatic, transcriptionally inert regions. In other words, the less-dominant subgenome carries a heavier load of the silencing apparatus, a finding that closely correlates with its reduced expression and helps explain why the Aj subgenome, relatively freed of these marks, dominates the transcriptome.

The story, however, is not a simple one-mark-one-outcome relationship. When the researchers examined how each epigenetic modification relates to gene expression individually and in combination, they found that expression levels are jointly regulated by synergistic and antagonistic interactions among multiple marks. Activating marks such as H3K4me3 and H3K27ac push genes toward high expression, repressive marks such as H3K27me3 and DNA methylation pull in the opposite direction, and the final transcriptional output of any given gene reflects the balance of these forces acting on its chromatin. This layered, combinatorial control means that subgenome dominance cannot be attributed to a single molecular switch; it emerges from the cumulative physics and chemistry of many marks working together or against each other along the chromosomes.

Transposable elements, the mobile DNA sequences often described as genomic parasites, turned out to be a second major axis of asymmetry. The team counted the copies of Class I transposable elements, retrotransposons that move through RNA intermediates, and found that the Bj subgenome harbors roughly three times as many of them as the Aj subgenome. The bias extends beyond copy number. The Bj subgenome carries a higher density of transposable elements inserted within gene bodies, and it hosts a greater number of Class I elements in the vicinity of genes. Because retrotransposon insertions tend to attract DNA methylation and H3K9me3, these insertional biases provide a mechanistic bridge between the element distributions and the epigenetic imbalance: a subgenome littered with more retrotransposons near its genes is also a subgenome more heavily methylated and more thickly marked with heterochromatin.

The picture that emerges is one in which the two parental subgenomes of B. juncea arrived at their current relationship partly through the historical accumulation of transposable elements. One genome, the Bj lineage, appears to have absorbed a substantially larger retrotransposon load, and the cell’s silencing machinery, deployed to keep those elements in check, spilled over into neighboring genes and depressed their expression. The other genome, Aj, with fewer insertions in and around its genes, escaped much of this collateral silencing and now supplies the dominant share of transcripts. The authors note that these insertional biases, together with their association with epigenetic modifications, may underlie the distinct regulatory landscapes that produce subgenome expression dominance, and their findings offer valuable insight into the epigenetic regulatory mechanisms operating in polyploid plants more broadly.

Why does this matter beyond evolutionary theory? Subgenome expression dominance plays a pivotal role in metabolic regulation, stress responses, environmental adaptation and the formation of agronomic traits, so knowing which molecular features mark out the dominant subgenome gives plant breeders and genome editors a map of where the cell’s transcriptional authority resides. Brown mustard is a widely cultivated and economically important oilseed and vegetable crop, and traits such as oil content, pungency and stress tolerance are all ultimately governed by which genes are transcribed and how strongly. If silencing marks and retrotransposon density are the levers that tilt expression between subgenomes, then manipulating those levers, for example by targeting methylation patterns or by using breeding strategies that shuffle the epigenetic load, could become a route to fine-tuning trait expression in allopolyploid crops.

The study also adds an important comparison point for polyploid biology in general. In other allopolyploids, including Brassica napus and various wheats, researchers have documented similar dominance relationships, and transposable element load has repeatedly surfaced as a candidate explanation. The B. juncea data strengthen the case that retrotransposon accumulation is not merely a symptom of genome aging but an active determinant of how two genomes negotiate their roles after merger. The combination of whole-genome bisulfite sequencing and ChIP-seq for multiple histone marks provides an unusually complete portrait of that negotiation in a single crop species, showing asymmetry in DNA methylation, in repressive histone methylation, and in the distribution of the very elements that recruit those marks. As genome assemblies and epigenomic datasets improve for more polyploid crops, the pattern seen here may prove to be a general rule: the genome that wins the expression contest is often the one that carries less ancient clutter and, consequently, less of the silencing apparatus that clutter attracts. For mustard farmers and genome biologists alike, the quiet war between two fused genomes is decided, in large part, by jumping genes and the methyl marks they leave behind.

Subject of Research: Epigenetic and transposable element basis of subgenome expression dominance in allotetraploid Brassica juncea

Article Title: Asymmetric epigenetic modifications and transposable elements contribute to subgenome expression dominance in allotetraploid Brassica juncea

Article References: Zhu, S., Li, G., & Wang, J. (2026). Asymmetric epigenetic modifications and transposable elements contribute to subgenome expression dominance in allotetraploid Brassica juncea. BMC Plant Biology. https://doi.org/10.1186/s12870-026-09981-x

Image Credits: AI Generated

DOI: 10.1186/s12870-026-09981-x

Keywords: Brassica juncea, subgenome expression dominance, DNA methylation, histone modification, transposable elements, epigenetics, allotetraploid, retrotransposons, H3K9me3, gene expression, polyploidy, plant genetics

Cellular senescence, the state in which cells permanently stop dividing but refuse to die, is a well-established driver of aging and a wide range of age-related pathologies. Senescent cells progressively accumulate in the tissues of aging mice and primates, and genetic or pharmacological clearance of these cells has been shown to extend both healthspan and longevity in naturally aged mice. Beyond aging itself, senescence is implicated in hepatic steatosis, obesity-associated metabolic syndrome, type I and type II diabetes, atherosclerosis, Alzheimer’s disease, and Parkinson’s disease. Decades of evidence have also linked aging to a relaxation of heterochromatin, the tightly packed, transcriptionally silent form of chromatin, and this loosening allows L1 elements to escape repression. The research team led by Anke Geng and Ying Jiang set out to determine whether SIRT1, whose protein levels decline during senescence and aging, directly guards the L1 genome and thereby influences the senescence program.

The investigators began with a well-characterized GFP-based reporter assay in HeLa cells, which quantifies L1 retrotransposition efficiency by detecting when an engineered L1 element successfully copies itself into the genome. When SIRT1 was overexpressed, retrotransposition dropped sharply; when SIRT1 was knocked down with siRNA, retrotransposition rose. At the transcriptional level, L1 mRNA declined roughly 30 percent in cells overexpressing SIRT1, while CRISPR/Cas9-mediated knockout of SIRT1 increased L1 transcription, a pattern reproduced in IMR90 primary fibroblasts and mouse embryonic fibroblasts. Because L1 transcription is initiated by an internal promoter within its 5-prime untranslated region, the team tested that promoter directly using luciferase reporters. SIRT1 inhibited 5-prime UTR activity in a dose-dependent manner, and its absence boosted promoter activity approximately twofold, an effect fully reversed by reintroducing the protein.

To connect this transcriptional control to genome integrity, the researchers exploited the fact that L1’s ORF2 protein induces DNA strand breaks as part of the retrotransposition process. Using the alkaline comet assay, a single-cell method that detects strand breaks and converts other lesions into breaks under alkaline conditions, the team measured genomic instability through the tail moment, a quantitative descriptor of DNA damage. SIRT1 overexpression reduced the tail moment in a dose-dependent fashion, whereas SIRT1 deficiency exacerbated ORF2-induced genomic instability. Re-expression of wild-type SIRT1 rescued the phenotype. Consistent with these results, SIRT1 overexpression lowered the accumulation of gamma-H2AX, a canonical marker of DNA double-strand breaks, while SIRT1 knockdown raised it. In a striking twist, two catalytically inactive mutants of SIRT1, G261A and H363Y, suppressed L1 5-prime UTR activity and genomic instability just as effectively as the wild-type protein, demonstrating that the protective role operates independently of the enzyme’s NAD+-dependent deacetylase activity.

The team then asked what happens to cellular senescence when SIRT1 levels change. They induced senescence in HCA2-hTERT fibroblasts and HeLa cells using X-ray irradiation at doses of 10 and 8 Gy, then stained for senescence-associated beta-galactosidase seven to ten days later. SIRT1 overexpression cut the fraction of senescent cells nearly in half, from about 30 percent to 13 percent in HCA2-hTERT cells and from 38 percent to 20 percent in HeLa cells, while SIRT1 knockdown raised senescence by an additional 10 percent. Levels of the senescence markers p21 and p16 fell with SIRT1 overexpression and climbed with its depletion. The senescence-associated secretory phenotype, the inflammatory cocktail secreted by senescent cells, was likewise damped by SIRT1, as measured by the expression of factors such as CCL2, MMP3, IL-1 alpha, IL-1 beta, and IL-6. Because L1 is known to activate the cGAS-STING innate immune pathway, the researchers examined phosphorylation of TBK1 and STING, finding both reduced by SIRT1 overexpression and elevated by its knockdown. Notably, lamivudine, also known as 3TC, a nucleoside reverse transcriptase inhibitor that potently blocks L1, attenuated the senescence induced by SIRT1 deficiency, confirming L1 as the causal culprit.

A key insight emerged from the biology of quiescence. Prior work established that L1 retrotransposition requires cell division, and the new study suggests why: in quiescent cells, SIRT1 piles up at L1 loci. Chromatin immunoprecipitation in mouse skeletal muscle satellite cells revealed significantly increased SIRT1 enrichment at L1 elements under quiescent conditions. In cultured IMR90-SVLT cells made quiescent by contact inhibition, confirmed by reduced EdU incorporation and diminished Ki67 expression, endogenous SIRT1 bound the L1 5-prime UTR at levels far exceeding those seen in proliferating cells. Correspondingly, L1 transcript levels dropped in quiescent cells, indicating that the cell-cycle dependence of L1 retrotransposition stems in part from transcriptional repression by accumulated SIRT1.

To uncover how SIRT1 enforces this repression, the team performed immunoprecipitation with an anti-SIRT1 antibody followed by liquid chromatography-tandem mass spectrometry, comparing quiescent and proliferating cells. The screen identified a set of SIRT1-interacting proteins involved in heterochromatin organization, most prominently the nuclear lamin protein Lamin B1 and the corepressor KAP1, and these interactions proved specific to quiescent conditions. Reciprocal co-immunoprecipitation confirmed the SIRT1-Lamin B1 interaction in HEK293FT cells, and experiments with purified recombinant proteins demonstrated that the two bind directly. Physical interaction between SIRT1 and KAP1 had been validated previously. Crucially, SIRT1 did not change the protein levels of either partner; instead, it acted as a molecular matchmaker, enhancing the interaction between Lamin B1 and KAP1, a cooperativity that collapsed in SIRT1-knockout cells.

Chromatin immunoprecipitation assays then traced the functional consequences at L1 loci. In control cells, both Lamin B1 and KAP1 occupied specific regions of the L1 promoter, but this binding was abolished in SIRT1-knockout cells. Because KAP1 is known to recruit the histone methyltransferase SETDB1, heterochromatin protein 1, and the NuRD complex to shape H3K9me3, the characteristic epigenetic mark of constitutive heterochromatin, the team assessed that mark directly. Global H3K9me3 decreased upon SIRT1 knockdown, and H3K9me3 enrichment at L1 promoters dropped correspondingly. The picture that emerges is elegant: SIRT1 binds the L1 5-prime UTR, recruits Lamin B1 and KAP1, stabilizes their partnership, and thereby maintains the repressive H3K9me3 landscape that silences L1 transcription. This places SIRT1 in a mechanistic lineage shared with, yet distinct from, its sirtuin siblings SIRT6 and SIRT7, which also restrain L1 through heterochromatin pathways. SIRT6 ADP-ribosylates KAP1 to promote its association with HP1 alpha, while SIRT7 deacetylates H3K18 to tether L1 to lamin proteins. The family has clearly converged on transposon silencing through divergent molecular routes.

The authors acknowledge that their senescence models are limited to stress-induced, rather than replicative, senescence, and that many mechanistic experiments were performed in transformed or immortalized cell lines rather than primary cells, questions that future work must address under physiological conditions. Nevertheless, the study delivers a compelling new framework. As SIRT1 declines during aging, the heterochromatin architecture protecting L1 elements erodes, dormant retrotransposons awaken, cytoplasmic L1 nucleic acids trip the cGAS-STING alarm, and the senescence program accelerates. Interventions that preserve or restore SIRT1 function, or that pharmacologically block L1 reverse transcriptase with drugs like lamivudine, could theoretically break this vicious cycle. In linking a longevity enzyme, a genomic parasite, and an immune sensor of misplaced DNA, the research illuminates one of the molecular threads that binds retrotransposon derepression to the aging clock, and offers concrete targets for therapies designed to delay aging and mitigate age-related disease.

Subject of Research: The role of SIRT1 in silencing L1 retrotransposons through stabilization of heterochromatin-modifying complexes during cellular senescence.

Article Title: SIRT1 Silences L1 Retrotransposons by Stabilizing Heterochromatin‐Modifying Complexes

Article References: Wang, X., Li, T., Tang, H., Liu, M. X., Peng, Q., Huang, X., Mao, Z., Jiang, Y., & Geng, A. (2026). SIRT1 Silences L1 Retrotransposons by Stabilizing Heterochromatin‐Modifying Complexes. Aging Cell, 25(9), Article e70689. https://doi.org/10.1111/acel.70689

Image Credits: AI Generated

DOI: 10.1111/acel.70689

Keywords: SIRT1, L1 retrotransposon, cellular senescence, heterochromatin, H3K9me3, Lamin B1, KAP1, cGAS-STING, aging, Aging Cell, sirtuins, genomic instability