Phased epigenomics and methylation inheritance in a historical Vitis vinifera hybrid

BACKGROUND: Epigenetic modifications, such as DNA methylation, regulate transcription and influence key biological traits. While many efforts were made to understand their stability in annual crops, their long-term persistence in clonally propagated plants remains poorly understood. Grapevine (Vitis vinifera) provides a unique model, with cultivars vegetatively propagated for centuries. RESULTS: Here, we assemble the phased genomes of Cabernet Sauvignon and its parental lineages, Cabernet Franc and Sauvignon Blanc, using HiFi long-reads and a gene map tenfold denser than existing maps. Using three clones per cultivar, we quantify methylation with very consistent short- and long-read sequencing and ensure both varietal representativeness and assessment of clonal variability. We leverage the parent-progeny sequence graph to highlight allele-specific methylation and conserved transcriptomic patterns for genes and small RNA. Such a format is essential to integrate multi-omics data and reveals that, despite less clonal conservation than genetic polymorphisms, methylation marks are remarkably inherited. By further demonstrating the linear-reference limitations, we determine that the correct representation of genetic variants by the sequence graph is crucial for the accurate allelic quantification of the methylome. CONCLUSIONS: These findings reveal the remarkable stability of epigenetic marks in a model propagated by asexual reproduction. Using a phased sequence graph, we introduce a scalable framework that accounts for genomic variation, accurately quantifies allele-specific methylation, and supports multi-omics integration such as our evaluation of the transcriptional impact of epigenetic inheritance. This approach has broad implications for perennial crops, where epigenetic variation could influence traits relevant to breeding, adaptation, and long-term agricultural sustainability.