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The rods of nocturnal mammals are unique among vertebrate cell types in having an 'inverted' nuclear architecture, with a single dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the nuclear periphery. We hypothesized that this unique chromatin organization would correlate with a unique epigenomic landscape as defined by chromatin accessibility. To test this idea, we performed open chromatin profiling (ATAC-seq) on purified mouse rods and their most closely related cell type, cone photoreceptors, which revealed that thousands of loci are selectively closed in rods. Comparison with open-chromatin maps from >60 additional cell types and tissues demonstrated that rods have by far the most closed chromatin architecture. To explore how the unique epigenomic landscape of rods is controlled, we profiled photoreceptors purified from mice lacking the rod master regulator Nrl. We find that the open-chromatin profile of Nrl-/- photoreceptors is nearly indistinguishable from that of native cones, indicating that Nrl is necessary to achieve selective chromatin closure in rods. Finally, we identified distinct enrichments of transcription factor binding sites in rods and cones, suggesting specific mechanisms by which rods and cones encode cell type-specific information in regulatory DNA. Taken together, these data provide new insight into the development and maintenance of photoreceptor identity, and highlight rods as an attractive system for studying the relationship between nuclear organization and local changes in chromatin accessibility. Overall design: ATAC-seq of adult (eight-week-old) mouse rods, green cones, and Nrl-/- photoreceptors (two biological replicates each) purified from transgenic reporter lines via fluorescence-activated cell sorting (FACS). RNA-seq of adult (eight-week-old) mouse rods and Nrl-/- photoreceptors (three biological replicates each) purified from transgenic reporter lines via FACS.</long_description><tag>xref:PubMed:28256534</tag><tag>xref:PubMed:31633482</tag><repository>ENA</repository><description_synonyms>HITS-CLIP, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, ChIP-Chip, Chromatin Immuno-precipitation, Laboratory, adult stage, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, Mus domesticus, mouse, ChIP Sequencing, RNA-seq, CLIP-Seq, Assay for Transposase-Accessible Chromatin Using Sequencing, ChIP-PET, House Mouse, ChIP-Exo, mice C57BL/6xCBA/CaJ hybrid, Mus muscaris, House, Mus, Chromatin Immunoprecipitation Sequencing-Chip, Mus musculus domesticus, Whole Transcriptome Shotgun Sequencing, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, Adults, Mice, adult, ChIA-PET, Mus musculus, Chromatin Immunoprecipitation Sequencing Chip, Laboratory Mice., Chromatin Immuno precipitation Sequencing, ATAC-seq assay, ChIP, Swiss, Chromatin Immunoprecipitation Paired End Tag, mice, ATAC-seq, Chromatin Immuno Precipitation Paired End Tag, Swiss Mouse, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, Chromatin Immunoprecipitation, House Mice, Swiss Mice, Chromatin Immuno-precipitation Sequencing, ChIP Exonuclease, ChIP-Seq, Sequencing, Assay for Transposase Accessible Chromatin Using Sequencing, domesticus, Chromatin Immunoprecipitation Paired-End Tag, Chromatin Immuno-Precipitation Paired-End Tag, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, Mouse, house mouse, ChIP-Exonuclease, Laboratory Mouse</description_synonyms><name_synonyms>Mus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse &lt;Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscaris</name_synonyms></additional><is_claimable>false</is_claimable><name>Mus musculus</name><description>ATAC-seq and RNA-seq of adult mouse rods and cones</description><dates><last_updated>2025-09-24</last_updated><first_public>2017-04-19</first_public></dates><accession>PRJNA325538</accession><cross_references><GEO>GSE83312</GEO><taxon>10090</taxon><PubMed>28256534</PubMed><PubMed>31633482</PubMed></cross_references></HashMap>