Integration of ATAC- and RNA-sequencing identifies chromatin and transcriptomic signatures in classical and non-classical zebrafish osteoblasts and indicates mechanisms of entpd5a regulation.

ATAC-seq and RNA-seq integration in zebrafish embryos identifies distinct chromatin and transcriptomic signatures in classical versus non-classical osteoblasts, linked to Dlx- and Hox-governed ossification programs.

• Why it matters: Bone formation in zebrafish requires two osteoblast types, but how chromatin regulation differs between them—and how entpd5a transcription is controlled—remains largely unknown.
• What they did: Using a newly generated transgenic line, classical and non-classical osteoblasts were isolated from embryos and profiled with ATAC-seq and RNA-seq, analyzed independently and integratively; the entpd5a promoter was mapped with resource-driven analysis and experimentally validated against ATAC-seq.
• The result: The study shows Dlx family factors are important for classical osteoblast regulation, while Hox family factors govern spinal ossification via non-classical osteoblasts, and it proposes spatio-temporally regulated promoter/enhancer interactions at the entpd5a locus.