Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


This content will become publicly available on September 9, 2026

Title: DNA methylation at retrotransposons protects the germline by preventing NRF1-mediated activation
Abstract Silencing evolutionary young retrotransposons by cytosine DNA methylation is essential for spermatogenesis, as failure to methylate their promoters leads to reactivation, meiotic failure, and infertility. How retrotransposons reactivate in the absence of DNA methylation is poorly understood. We show that upon defective DNA methylation, distinct retrotransposon families display unique expression patterns and chromatin landscapes during mouse spermatogenesis. We find that their reactivation in meiotic spermatocytes correlates with the loss of bivalent H3K4me3-H3K27me3 chromatin marks. Through proteomics and chromatin profiling, we identify NRF1 as a DNA methylation-sensitive transcription factor that transactivates unmethylated retrotransposons. Conditional germline knockout ofNrf1in the absence of DNA methylation rescues the silencing of the most mutagenic retrotransposon in mice, namely Intracisternal A-particle or IAP. Our findings reveal that chromatin modifications together with a DNA methylation-sensitive transcription factor regulate retrotransposon expression in the absence of DNA methylation in spermatogenesis, revealing a mechanism by which retrotransposons proliferate in the germline after evading DNA methylation-based silencing.  more » « less
Award ID(s):
2042908
PAR ID:
10671859
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Springer Nature
Date Published:
Journal Name:
EMBO Reports
Volume:
26
Issue:
17
ISSN:
1469-3178
Page Range / eLocation ID:
4312 to 4339
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; (, PLOS Genetics)
    Springer, Nathan M. (Ed.)
    DNA methylation plays crucial roles in transposon silencing and genome integrity. CHROMOMETHYLASE3 (CMT3) is a plant-specific DNA methyltransferase responsible for catalyzing DNA methylation at the CHG (H = A, T, C) context. Here, we identified a positive role of CMT3 in heat-induced activation of retrotransposonONSEN. We found that the full transcription ofONSENunder heat stress requires CMT3. Interestingly, loss-of-function CMT3 mutation led to increased CHH methylation atONSEN. The CHH methylation is mediated by CMT2, as evidenced by greatly reduced CHH methylation incmt2andcmt2 cmt3mutants coupled with increasedONSENtranscription. Furthermore, we found more CMT2 binding atONSENchromatin incmt3compared to wild-type accompanied with an ectopic accumulation of H3K9me2 under heat stress, suggesting a collaborative role of H3K9me2 and CHH methylation in preventing heat-inducedONSENactivation. In summary, this study identifies a non-canonical role of CMT3 in preventing transposon silencing and provides new insights into how DNA methyltransferases regulate transcription under stress conditions. 
    more » « less
  2. ; ; ; ; ; (, bioRxiv)
    ABSTRACT RNAs in circulation carry sequence-specific regulatory information between cells in plant, animal, and host-pathogen systems. Such RNA can cross generational boundaries, as evidenced by somatic double-stranded RNA (dsRNA) in the nematodeC. eleganssilencing genes of matching sequence in progeny. Here we dissect the intergenerational path taken by dsRNA from parental circulation and discover that cytosolic import through the dsRNA importer SID-1 in the parental germline and/or developing progeny varies with developmental time and dsRNA substrates. Loss of SID-1 enhances initiation of heritable RNA silencing within the germline and causes changes in the expression of thesid-1-dependentgenesdg-1that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear Z granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop reveals how retrotransposons could persist by hosting genes that regulate their own silencing. 
    more » « less
  3. ; ; ; ; (, Genome Biology)
    Abstract BackgroundIn several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance remains unclear. ResultsWe report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range indrddmutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity. ConclusionsWe propose a new model for GbM in regulating gene expression plasticity, including a novel type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state. 
    more » « less
  4. ; ; ; ; ; ; (, Plant Direct)
    Abstract Plant chromatin dynamics are generally recognized as playing a role in the genomic response to environmental stress. Although stress‐induced transcriptional activities of LTR‐retrotransposons have been reported, whether the stress response can be detected at the level of chromatin structure for LTR‐retrotransposons is largely unknown. Using differential nuclease sensitivity profiling, we identified that two out of 29 maize LTR‐retrotransposon families change their chromatin structure in response to drought stress in leaf tissue. The two LTR‐retrotransposon families,ulohandvegu, are classified as nonautonomous LTR‐retrotransposons. Differently from other families, the chromatin structure of these two families shifted from more open in normal conditions to more closed following drought stress. Althoughulohandvegulack sequence similarity, most of them shared an intriguing feature of having a new and uncharacterized insertion of a DNA sequence near one side of an LTR. In theulohfamily, nine members with a strong drought response also exhibited a drought‐induced reduction of published H3K4me3 histone modification in the inserted DNA region, implicating this modification in the chromatin structural changes. Our results provide new insight into how LTR‐retrotransposons can alter their chromatin structure following stress response in plants. 
    more » « less
  5. ; ; (, Proceedings of the National Academy of Sciences)
    The rate and spectrum of somatic mutations can diverge from that of germline mutations. This is because somatic tissues experience different mutagenic processes than germline tissues. Here, we use nanorate sequencing (NanoSeq) to identify somatic mutations inArabidopsisshoots with high sensitivity. We report a somatic mutation rate of 3.6 × 10−8mutations/bp, ~2 to 7× measured germline mutation rates. Somatic mutations displayed elevated signatures consistent with oxidative damage, UV damage, and transcription-coupled nucleotide excision repair. Both somatic and germline mutations were enriched in transposable elements and depleted in genes, but this depletion was greater in germline mutations. Somatic mutation rate correlated with proximity to the centromere, DNA methylation, chromatin accessibility, and gene/TE content, properties which were also largely true of germline mutations. We note that DNA methylation and chromatin accessibility have different predicted effects on mutation rate for genic and nongenic regions; DNA methylation associates with a greater increase in mutation rate when in nongenic regions, and accessible chromatin associates with a lower mutation rate in nongenic regions but a higher mutation rate in genic regions. Together, these results characterize key differences and similarities in the genomic distribution of somatic and germline mutations. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Text Encoded Conversion
  • XML
  • Save / Share this Record
  • Send to Email