Suzanne de Bruijn

178 Chapter 4 LINC01476 55 _ 0 _ 200 _ 0 _ 0 _ -5 _ 55 _ 0 _ 55 _ 0 _ 55 _ 0 _ 55 _ 0 _ 55 _ 0 _ 10.0 20.0 0.0 CTCF Retina-specific expression H3K27ac ATAC-seq NRL CRX OTX2 Retinal organoid Hi-C map A B Human retina ChIP-seq and RNA-seq data C LINC01476 B B YPEL2 TAD B Retinal enhancer Boundary SMG8 GDPD1 Scale chr17: 200 kb hg19 57,300,000 57,400,000 57,500,000 57,600,000 57,700,000 SKA2 PRR11 SMG8 GDPD1 YPEL2 MIR4729 DHX40 CLTC PTRH2 VMP1 Figure 3. YPEL2 is located within a structured active compartment that contains retinal-specific enhancers. (A) The TAD landscape of the genomic region disrupted by the RP17-SVs. Hi-C map of control retinal organoids revealed a structured domain containing YPEL2 (B) YPEL2 TAD boundaries correspond with CTCF sites identified in human retina. Analysis of RNA-seq and assay for transposase accessible chromatin using sequencing (ATAC)-seq data across the YPEL2 region shows YPEL2 retinal expression and an accessible chromatin configuration. Analysis of H3K27Ac ChIP-seq data in the same region revealed several active enhancers located within the YPEL2 TAD, which are enriched for retinal transcription factor binding sites, including NRL, CRX, and OTX2 (Cherry et al. 2020). 27 These enhancers were located 5’ of the CTCF boundary site within LINC01476. (C) Schematic representation of the YPEL2 TAD structure.