@inproceedings{01HT25YGBJR3PE3WQ8W45B3JXX,
  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). Many 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 3D genome topology 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 using both Hi-C and HiChIP data revealed that almost 60% of known IRD genes were marked by differential 3D genome structure and/or cis-regulatory interactions. Next, we used UMI-4C to zoom in on regulatory chromatin interactions at the ABCA4 locus, which is implicated in the most common autosomal recessive IRD. 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 at retinal disease loci, but also delineate the search space for non-coding genomic variation underlying unsolved IRD.}},
  author       = {{D'haene, Eva and Lopez Soriano, Victor and Martinez-Garcia, Pedro Manuel and Kalayanamontri, Soraya and Dueñas Rey, Alfredo and Sousa-Ortega, Ana and Naranjo, Silvia and Van de Sompele, Stijn and Vantomme, Lies and Mahieu, Quinten and Vergult, Sarah and Gomez-Skarmeta, José-Luis and Martinez-Morales, Juan Ramon and Bauwens, Miriam and Tena, Juan J. and De Baere, Elfride}},
  booktitle    = {{ASHG 2023 Annual Meeting, Abstracts}},
  language     = {{eng}},
  location     = {{Washington, DC, USA}},
  title        = {{Comparative 3D genome analysis between neural retina and RPE reveals diferential cis-regulatory interactions at retinal disease loci}},
  year         = {{2023}},
}