Epigenomic landscapes of retinal rods and cones.

Alisa Mo,Gilbert L Henry,Serge Picard,Ryan Lister,Sean R Eddy,Joseph R Ecker,Mark A Urich,Eran A Mukamel,Jeremy Nathans,Chongyuan Luo,Michael A Beer,Fred P Davis,Joseph R Nery

doi:10.7554/elife.11613

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.

Highlights

The retina is the starting point of vision
Using previously defined criteria (Stadler et al, 2011; Burger et al, 2013), we identified two types of regions that are depleted for DNA methylation: (1) 16617 rod and 15888 cone discrete (
We identified a set of 55366 regions in rods and 75650 regions in cones with increased ATACseq densities that mark accessible chromatin (Supplementary file 3)

Summary

Introduction

The retina is the starting point of vision. It originates from the embryonic diencephalon and contains three layers of neurons: an outer nuclear layer with rods and cones; an inner nuclear layer with bipolar, horizontal, and amacrine cells; and a ganglion cell layer (Swaroop et al, 2010). Photoreceptor specialization results from well-defined rod- and cone-specific patterns of gene expression (Kefalov, 2012; Siegert et al, 2012), which are in part controlled by retinal transcription factors (TFs) OTX2, CRX, NRL, and NR2E3.

Methods

Results

Conclusion