Epigenomic landscapes of retinal rods and cones

Abstract

Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks, transcription factor binding, and DNA sequence motifs. Loss of NR2E3 in rods shifts their epigenomes to a more cone-like state. The data further reveal wide differences in DNA methylation between retinal photoreceptors and brain neurons. Surprisingly, we also find a substantial fraction of DNA hypo-methylated regions in adult rods that are not in active chromatin. Many of these regions exhibit hallmarks of regulatory regions that were active earlier in neuronal development, suggesting that these regions could remain undermethylated due to the highly compact chromatin in mature rods. This work defines the epigenomic landscapes of rods and cones, revealing features relevant to photoreceptor development and function.DOI: http://dx.doi.org/10.7554/eLife.11613.001

Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15

“…the accessibility of this region of the Rho promoter (14). Thus, these previous results represent a reference system to determine whether somatic ectopic gene transfer of a TF might be used to silence RHO expression.…”

“…In addition, KRAB-ZNF TFs show highly differential tissue patterns of expression (27,28). Thus, in principle, this TF somatic ectopic gene transfer approach could be extended to other gene targets by combining TF preferences with cell-specific expression and genome accessibility maps (10,14). Of note, gene expression profiles in diverse tissues of the human body and across individuals are being increasingly identified (29).…”

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

“…Among the significantly altered transcripts in P8 Opn4 DTA/DTA versus wild-type retinas, the dopamine receptor D 4 (Drd4) appeared to be a good candidate, showing significantly reduced expression (Figure 2B). DRD4 expression was confirmed to be expressed in cones in four separate transcriptional datasets (Hughes et al, 2017; Kim et al, 2016; Mo et al, 2016; Siegert et al, 2012). In the mature retina, ipRGCs are known to influence cone photoreceptor light adaptation by controlling dopamine (DA) release from dopaminergic amacrine cells (DACs) (Prigge et al, 2016; Zhang et al, 2008a), an effect dependent on the expression of DRD4 (Jackson et al, 2012).…”

Lessons from Retinoblastoma: Implications for Cancer, Development, Evolution, and Regenerative Medicine

“…We propose that one underlying mechanism of cellular pliancy is the organization of the epigenome (Figure 3). As neurons in the retina undergo cell fate specification, they reorganize their epigenome to support retinal differentiation and cellular homeostasis [58, 59]. Clearly, the genes that are expressed in the differentiating neurons are in an active chromatin state.…”