Epigenetic Coalitions Couple Tissue Growth to Generate Periodic Colour Patterns in Birds
Periodic patterning is fundamental to biological organization. In birds, colour stripes and spots on growing embryonic surface and elongating feather filaments provide a unique system to study continuous periodic patterning in expanding domains. Agouti-signaling protein (ASIP) directly reports epigenomic activity during colour patterning. Using a neural-network-like architecture, we show that ASIPs cis-regulatory landscape functions as hidden layers, integrating morphogen feedback, chromatin topology, and tissue geometry to generate discrete colour outputs. Single-nucleus multiome and Micro-C uncover stage- and context-specific enhancer-silencer coalitions. Epidermal Wnt ligands activate ASIP while inducing Wnt inhibitors in fibroblasts, forming a negative-feedback loop coupling periodic patterning to domain expansion. Comparative cross-tissue and cross-species analyses define cis-regulatory modules comprising an epigenetic grammar; functional assays highlight retrotransposon co-option expanding ASIPs cis-regulatory repertoire, potentially contributing to colour pattern evolution. Together, these findings motivate a Turing-principle-based communication model: ASIP reflects epigenetic coalitions shifting to drive diverse, environmentally tunable colour motifs for adaptation.