Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation

Abstract

To analyze cell lineage-specific transitions in global transcriptional and epigenetic changes during retinogenesis, we purified retinal cells from normal mice during postnatal development into two fractions, namely, photoreceptors and other retinal cells, based on Cd73 expression, and performed RNA sequencing and ChIP sequencing of H3K27me3 and H3K4me3. Genes expressed in the photoreceptor lineage were marked with H3K4me3 in the Cd73-positive cell fraction; however, the level of H3K27me3 was very low in both Cd73-positive and -negative populations. H3K27me3 may be involved in spatio-temporal onset of a subset of bipolar-related genes. Subsets of genes expressed in amacrine and retinal ganglion cells, which are early-born retinal cell types, were suggested to be maintained in a silent state by H3K27me3 during late-stage retinogenesis. In the outer nuclear layer, upregulation of Rho and rod-related genes were observed in Ezh2-ablated retina, suggesting a role for H3K27me3 in the maintenance of proper expression levels. Taken together, our data on the transition of lineage-specific molecular signatures during development suggest that histone methylation is involved in retinal differentiation and maintenance through cell lineage-specific mechanisms.

Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse

“…Retinalspecific ablation of Ezh2 leads to acceleration of photoreceptor terminal differentiation with premature expression of key photoreceptor genes in the postnatal retina (22,24). Dynamics of Ezh2 expression in the developing cochlear sensory epithelium also point to a regulatory role in terminal differentiation (34), but no similar data are available in the olfactory epithelium at present.…”

“…Interestingly, most of the early-onset retinal genes identified to be repressed at P5 in the KO (Fig. 6 A and B) are downstream targets of Ezh2 (22,24,25). Delayed up-regulation of Rho expression in the KO was also confirmed by immunostaining on P12 and P16 (Fig.…”

“…We first inspected temporal expressions of retinal genes potentially involved in driving terminal differentiation events (22) and identified a group of early-onset genes in the retina of KO mice that were initially repressed at P5 and gradually rose back to near wild-type levels by P27 (Fig. 6 A and B).…”

Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation

“…This at the first glance seems highly unlikely, knowing the successive events necessary for cone commitment13, 27 and the epigenetic modifications occurring in rods and cones after their differentiation 45, 46. It was, nonetheless, recently shown that the downregulation of NRL in the adult retina provokes a cone-like phenotype with rod characteristic defects 47 .…”

Retina Development in Vertebrates: Systems Biology Approaches to Understanding Genetic Programs

“…In this work the authors described a unique epigenetic signature marking rod photoreceptor‐specific genes. The concept of a pattern of histone modifications specific of a particular cell type has also been explored by Ueno and collaborators . They discovered that photoreceptor‐specific loci were also marked by H3K4me3.…”