Comparative 3D genome analysis between neural retina and RPE reveals differential cis -regulatory interactions at retinal disease loci
Comparative 3D genome analysis between neural retina and RPE reveals differential cis -regulatory interactions at retinal disease loci
ABSTRACT Vision depends on the functional interplay between the photoreceptor cells of the neural retina and the supporting cells of the underlying retinal pigment epithelium (RPE). Most genes involved in inherited retinal diseases (IRD) display highly specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. To understand the role of differential chromatin architecture in establishing tissue-specific expression patterns at IRD loci in the human neural retina and the RPE, we mapped genome-wide chromatin interactions by applying in situ Hi-C and H3K4me3 HiChIP to human adult post-mortem donor retinas. A comparative 3D genome analysis between neural retina and RPE/choroid revealed that almost 60% of 290 known IRD genes were marked by differential 3D genome structure and/or cis-regulatory interactions. One of these genes was ABCA4, which is implicated in the most common autosomal recessive IRD. We zoomed in on tissue-specific chromatin interactions at the ABCA4 locus using high-resolution UMI-4C assays. Upon integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish, we revealed tissue-specific CREs interacting with ABCA4. In summary, through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, we have shown that gene regulation at key IRD loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes of IRD genes, but also delineate the search space for non-coding genomic variation underlying unsolved IRD. biorxiv;2023.06.20.543842v1/UFIG1F1ufig1
D?ˉhaene Eva、Soriano Victor L¨?pez、Kalayanamontri Soraya、Naranjo Silvia、Van de Sompele Stijn、Vantomme Lies、Mahieu Quinten、Vergult Sarah、G¨?mez-Skarmeta Jos¨| Luis、Mart¨anez-Garc¨aa Pedro Manuel、Sousa-Ortega Ana、Mart¨anez-Morales Juan R.、Bauwens Miriam、Due?as Rey Alfredo、De Baere Elfride、Tena Juan J.、Neto Ana Bastos
Department of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalDepartment of Biomolecular Medicine, Ghent University||Center for Medical Genetics, Ghent University HospitalCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de OlavideCentro Andaluz de Biolog¨aa del Desarrollo, Consejo Superior de Investigaciones Cient¨aficas and Universidad Pablo de Olavide
眼科学基础医学生物科学研究方法、生物科学研究技术
3D genomeHi-CHiChIPUMI-4Chuman retinaneural retinaretinal pigment epitheliuminherited retinal diseaseABCA4cis-regulatory elementsenhancer assaysgene regulation
D?ˉhaene Eva,Soriano Victor L¨?pez,Kalayanamontri Soraya,Naranjo Silvia,Van de Sompele Stijn,Vantomme Lies,Mahieu Quinten,Vergult Sarah,G¨?mez-Skarmeta Jos¨| Luis,Mart¨anez-Garc¨aa Pedro Manuel,Sousa-Ortega Ana,Mart¨anez-Morales Juan R.,Bauwens Miriam,Due?as Rey Alfredo,De Baere Elfride,Tena Juan J.,Neto Ana Bastos.Comparative 3D genome analysis between neural retina and RPE reveals differential cis -regulatory interactions at retinal disease loci[EB/OL].(2025-03-28)[2025-06-28].https://www.biorxiv.org/content/10.1101/2023.06.20.543842.点此复制
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