Zebrafish (Danio rerio) display a remarkable switch in their ribosome composition, as two divergent subtypes of 45S ribosomal RNAs are differentially transcribed during development. The maternal 45S genes are expressed in oocytes and enriched in the egg and the early embryo. The somatic 45S genes are expressed after zygotic genome activation and are transcribed in virtually all adult tissues. Strikingly, somatic 45S genes are constitutively hypermethylated even when actively transcribed. Further, PacBio HiFi reads demonstrated that these genes are hypermethylated with single-repeat resolution. Hence, this unexpected finding challenges our understanding of how methylation impacts gene expression and heterochromatin formation. We are working to dissect the relationship of DNA methylation, chromatin accessibility, histone modifications, and transcription factor binding in somatic and maternal 45S genes. Understanding this relationship will inform models for spatiotemporal control of heterochromatin, genome organization, and the ribosomal developmental switch in zebrafish.