The Association Between DNA Methylation and Three-Dimensional Genome During Whole Genome Doubling in Arabidopsis...

Whole genome doubling (WGD) triggers profound genomic and epigenetic reorganization, yet the functional dynamics of DNA methylation during this process remain incompletely resolved. Here, we integrate whole genome bisulfite sequencing (WGBS) and three-dimensional chromatin interaction data to display methylation landscapes in autotetraploid Arabidopsis thaliana. Our analysis reveals evolutionarily conserved spatial patterning of DNA methylation after WGD, with centromeric enrichment and telomeric depletion. Chromosome-level profiling identifies Chromosome 2 as the most highly methylated across CG, CHG, and CHH contexts, while Chromosome 1 shows the lowest methylation. Subcontext methylation analysis uncovers increases in methylation levels in autotetraploid Arabidopsis thaliana, most pronounced in the CHH context, yet global distribution patterns remain stable. Comparative methylation profiling around genes and transposable elements (TEs) reveals elevated CHH methylation in autotetraploid gene bodies and flanking regions, whereas TE bodies exhibit minimal changes despite minor flanking hypermethylation. Strikingly, 8% of chromatin compartments were restructured, and B-B interactions weakened in autotetraploid, while DNA methylation remained stable across shifting A/B compartments. Our findings suggest that DNA methylation serves as a resilient epigenetic modification during WGD, even if 3D chromatin architecture undergoes reorganization upon WGD in some degree.