Aberrant homeodomain–DNA cooperative dimerization underlies distinct developmental defects in two dominant CRX retinopathy models

CRX E80A differential activity at monomeric and dimeric K₅₀ HD motifs contributes to gene misexpression at different stages of photoreceptor development. (A) Diagrams of photoreceptor genes regulated solely by monomeric K₅₀ HD motifs (top) or combinationally by monomeric and dimeric K₅₀ HD motifs (bottom). For simplicity, representative motif logos are shown. The relative position of the motifs is arbitrary. (B) Heatmap comparing the CRX-DAG expression changes in the Crx^E80A/A retinas at ages of postnatal day (P) 10 and P21. The gene sets in the heatmaps are as defined in A. (C,D) Schematics demonstrating the K₅₀ HD division-of-labor model in regulating photoreceptor epigenome and transcriptome at different stages of development.