Fig. 5: Identification of a retina-specific Crb1 isoform in mouse and human retina.

Transcript maps of most abundant Crb1 isoforms from mouse retina (a) and cortex (b). Map depicts reverse strand of mouse chromosome 1 at indicated location (Mb, megabase). 5′ and 3′ ends of Crb1 transcripts are indicated. A is the canonical isoform; A2 is a minor splice variant of A. These isoforms are shared between retina and cortex, whereas Cortex 1, Cortex 2, and Crb1-B are tissue-specific. Corresponding exon coverage (dark blue) and sashimi plots (red lines) were generated from lrCaptureSeq dataset. Note prevalence of reads associated with Crb1-B isoform (a). c Assay for chromatin accessibility (ATAC-seq; GSE102092, GSE83312) identifies likely promoters of Crb1-A and -B isoforms. Colored bars indicate location of putative A (green) and B (blue) promoters. Maps in a–c are aligned with each other. Crb1-A promoter is more open during development, but stays accessible in mature retina. Crb1-B promoter is open and presumed active in mature rods and both types of cones. Dnase I hypersensitivity data from ENCODE project reveals distinct chromatin environment in frontal cortex, consistent with expression of A isoform, as well as shorter cortex isoforms (cortex 1 and 2; gray bar at top). d Transcript maps of most abundant human retinal CRB1 isoforms, identified by lrCaptureSeq. Map depicts forward strand of human chromosome 1 at indicated location. A and B isoforms are highly homologous to mouse (a). CRB1-C encodes a putative secreted form of the protein; it was also identified in the mouse dataset but its relative abundance in mouse was much lower than A and B. Note that Crb1-A2 was not detected in the human dataset. Exon coverage (dark blue) and sashimi plots (red lines) were generated from lrCaptureSeq data. e ATAC-seq (GSE99287) of human peripheral (per.) and macular (mac.) retina show open regulatory sites corresponding to putative promoters for CRB1-A (green bar) and CRB1-B (blue bar). Two biological replicates are shown. Maps in d, e are aligned with each other.