Epigenomic Profiling and Single_Nucleus_RNA_Seq of Adult Human Retina, Macula, and RPE/Choroid

Cis_regulatory elements (CREs) orchestrate the dynamic and diverse transcriptional programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. However, the cellular complexity of the human brain has largely precluded the identification of functional regulatory variation within the human CNS. We took advantage of the retina, a well_characterized region of the CNS with reduced cellular heterogeneity, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive resource of tissue_specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue_specific gene expression programs and defines the regulatory elements with the potential to contribute to mendelian and complex disorders of human vision. Overall design: ATAC_Seq was performed on 8 adult human retina and 3 macula samples; ChIP_Seq for histone modifications on 3 adult human retina, 3 macula, and 2 retina pigment epithelium/choroid samples; ChIP_Seq for 5 different transcription factors on adult human retina samples; RNA_Seq from cellular nuclei from 7 adult human retina, 3 macula, and 3 retinal pigment epithelium/choroid samples; single nucleus RNA_seq from 3 adult human retina samples.