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Elife. 2016 Mar 7;5:e11613. doi: 10.7554/eLife.11613.

Epigenomic landscapes of retinal rods and cones.

Author information

1
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States.
2
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.
3
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
4
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States.
5
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
6
Department of Cognitive Science, University of California San Diego, La Jolla, United States.
7
The ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, Australia.
8
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States.
9
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States.
10
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, United States.
11
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.

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.

KEYWORDS:

DNA methylation; chromatin; evolutionary biology; genomics; mouse; neuroscience; retinal development; retinal photoreceptors; transcription factors

PMID:
26949250
PMCID:
PMC4798964
DOI:
10.7554/eLife.11613
[Indexed for MEDLINE]
Free PMC Article

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