Chromatin accessibility landscape of a parasitic nematode during embryogenesis.

backgroundChromatin accessibility is a fundamental determinant of genome regulation, enabling transcription factors and RNA polymerase to bind DNA and drive developmental programs. While accessibility landscapes have been studied in model organisms such as Caenorhabditis elegans, almost nothing is known about the regulatory architecture of parasitic nematodes.

resultsWe used assay for transposase-accessible chromatin with sequencing (ATAC-seq) to characterise the first genome-wide chromatin accessibility map for Haemonchus contortus - a major pathogen of ruminants and a key model organism for the parasitic nematode order Strongylida, which includes many pathogens of humans and animals. Analysis of embryonated eggs produced ~ 700 million high-confidence reads and identified 22,922 reproducible 'open' chromatin regions. Promoter accessibility was concentrated around transcription start sites and defined 3,897 promoter-accessible genes (~ 20% of the genome). These genes were highly enriched in developmental processes and signalling pathways, including Hippo, Rap1 and FOXO, and showed significantly higher expression across cell types compared with inaccessible genes. Accessible promoters also corresponded disproportionately to genes predicted to be essential, as supported by two independent computational frameworks. Integration with co-expression networks revealed enrichment of promoter-accessible genes in modules linked to translation, protein targeting and proteostasis. Motif analysis identified 378 enriched motifs representing ~ 100 transcription factors, dominated by Homeobox, bHLH, nuclear hormone receptor and Forkhead families, all known regulators of embryogenesis.

conclusionThis study defines the first chromatin accessibility landscape for a parasitic nematode and delivers a resource for investigating developmental regulation, adaptation and host-parasite interactions.