Christy Luong

All Publications

• Single-cell multiome of the human retina and deep learning nominate causal variants in complex eye diseases. Cell genomics Wang, S. K., Nair, S., Li, R., Kraft, K., Pampari, A., Patel, A., Kang, J. B., Luong, C., Kundaje, A., Chang, H. Y. 2022; 2 (8)

  Abstract

  Genome-wide association studies (GWASs) of eye disorders have identified hundreds of genetic variants associated with ocular disease. However, the vast majority of these variants are noncoding, making it challenging to interpret their function. Here we present a joint single-cell atlas of gene expression and chromatin accessibility of the adult human retina with more than 50,000 cells, which we used to analyze single-nucleotide polymorphisms (SNPs) implicated by GWASs of age-related macular degeneration, glaucoma, diabetic retinopathy, myopia, and type 2 macular telangiectasia. We integrate this atlas with a HiChIP enhancer connectome, expression quantitative trait loci (eQTL) data, and base-resolution deep learning models to predict noncoding SNPs with causal roles in eye disease, assess SNP impact on transcription factor binding, and define their known and novel target genes. Our efforts nominate pathogenic SNP-target gene interactions for multiple vision disorders and provide a potentially powerful resource for interpreting noncoding variation in the eye.

  View details for DOI 10.1016/j.xgen.2022.100164

  View details for PubMedID 36277849

• Xist nucleates local protein gradients to propagate silencing across the X chromosome CELL Markaki, Y., Chong, J., Wang, Y., Jacobson, E. C., Luong, C., Tan, S. X., Jachowicz, J. W., Strehle, M., Maestrini, D., Banerjee, A. K., Mistry, B. A., Dror, I., Dossin, F., Schoeneberg, J., Heard, E., Guttman, M., Chou, T., Plath, K. 2021; 184 (25): 6174-+

  Abstract

  The lncRNA Xist forms ∼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain ∼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.

  View details for DOI 10.1016/j.cell.2021.10.022

  View details for Web of Science ID 000730753900003

  View details for PubMedID 34813726

  View details for PubMedCentralID PMC8671326