Biology subjects

Pigeon, A.

Publications and source records attributed to Pigeon, A..

3 recordsLinked to original sources

bioRxiv2026

DNA methylation links lagging strand replication to transposable element control

DNA methylation is an essential epigenetic mark that silences transposable elements (TEs) in mammalian genomes1,2. Following DNA replication, methylation patterns must be faithfully restored3,4, yet how the two processes are coordinated remains unclear. Here, using strand-specific, genome-wide analyses5-7 in mouse embryonic stem cells, we show that DNA methylation maintenance is coupled to the lagging-strand synthesis in TE-rich regions. Paradoxically, despite this targeting, the lagging strand is more permissive for TE integration than the leading strand. Notably, insertions of full-length LINE-1s, SINEs, and satellite repeats are all enriched on the lagging strand over evolutionary time. Consequently, most TEs, particularly young elements, are oriented head-on relative to replication forks in the mouse genome, creating an unfavorable genomic configuration8 that is preferentially targeted by DNA methylation maintenance. Mechanistically, DNA methylation maintenance is coupled to the lagging-strand replication via UHRF1-LIG19 and PCNA-PAF1510 interactions, and the interference in this mechanism slows Okazaki fragment maturation, and thereby potentially may facilitate TE retention. Together, we show a mechanism of TE control during DNA replication with an unexpected evolutionary interplay in which DNA methylation may facilitate, rather than solely prevent, TE expansion.

Molecular Biology↗

bioRxiv2025

Characterization of interindividual DNA methylation variability in rainbow trout (Oncorhynchus mykiss)

Interindividual epigenetic variability, particularly in DNA methylation, is now recognized as a significant contributor to phenotypic diversity in humans and mammals. These epivariable regions, which make up a small fraction of the genome, are strongly influenced by genetic factors and environmental factors, especially during early development. In this context, epigenetic variability of DNA methylation has been proposed as an adaptive force involved in various environmental responses. In fish and other vertebrates, environmental factors are known to influence the health, performance and welfare, likely through the alteration of the epigenetic landscape. However, whether interindividual epigenetic variability may contribute to the phenotypic plasticity of fishes is unknown. Here we provide a first description of the rainbow trout methylome variability using a whole-genome bisulfite sequencing approach in an isogenic line to minimize genetic variation. Variable methylation regions were identified in both liver and hypothalamus tissues of 12 replicate fishes and were found enriched at gene regulatory elements, such as promoters and first introns. Gene Ontology analysis revealed functional clusters related to cellular development, neural communication, metabolic balance, and immune response. Interestingly, some variably methylated regions are found at the same genomic loci in both tissues and showed a strong intraindividual correlation in methylation levels, suggesting establishment during early embryogenesis. Overall, our work demonstrates the existence of interindividual epigenetic variability in rainbow trout and provides valuable insights into the regulatory function of DNA methylation variation that is likely involved in developmental and physiological processes.

genomics↗

bioRxiv2019

Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq)

Long interspersed element-1 retrotransposons (LINE-1 or L1) are ~6 kb mobile DNA elements implicated in the origins of many Mendelian and complex diseases. The actively retrotransposing L1s are mostly limited to the L1 human specific Ta subfamily. In this manuscript, we present REBELseq as a method for the construction of differentially amplified next-generation sequencing libraries and bioinformatic identification of Ta subfamily long interspersed element-1 human specific elements. REBELseq was performed on DNA isolated from NeuN+ neuronal nuclei from postmortem brain samples of 177 individuals and empirically-driven bioinformatic and experimental cutoffs were established. REBELseq reliably identified both known and novel Ta subfamily L1 insertions distributed throughout the genome. Differences in the proportion of individuals possessing a given reference or non-reference retrotransposon insertion were identified. We conclude that REBELseq is an unbiased, whole genome approach to the amplification and detection of Ta subfamily L1 retrotransposons.

genetics↗