Extended Data Fig. 2: Examples of enhancer—promoter interactions linked to congenital disorders.
From: Increased enhancer–promoter interactions during developmental enhancer activation in mammals
a, Hs1507 limb enhancer (green) located in the non-coding region which is duplicated in patients with polydactyly (pink bar indicates the homologous region in the mouse genome)8. Hs1507 forms significant chromatin interactions with the promoter of the Epha4 (blue line) located ~1.5 Mb away. Shown is the Epha4 genomic region (chr1:74,788,119-77,634,678; mm10). b, Many de novo rare variants identified in patients with preaxial polydactyly101 are located in the ZRS limb enhancer (green bar) which forms significant interactions with the promoter of Shh located ~850 kb away. Shown is the Shh (blue line) genomic region (chr5:28,320,000-29,400,000; mm10). c, Hs1877 face enhancer (green) located in the non-coding region containing 146 SNPs found in patients with cleft lip risk (purple bar indicates the homologous region in the mouse genome)102. Hs1877 forms significant chromatin interactions with the promoter of the Myc (blue line) located ~900 kb away in the face. The Myc genomic region (chr15:61,880,003-63,506,895; mm10). d, Three de novo rare variants identified in patients with autism are located in the hs737 midbrain/hindbrain enhancer (green bar)103,104, which forms strong significant interactions with the promoter of Ebf3 (blue line) located ~1,000 kb away in the midbrain. Shown is the Ebf3 genomic region (chr7:136,018,204-137,420,338; mm10). Red arrowheads indicate capture Hi-C viewpoints.
