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| Status |
Public on Apr 08, 2020 |
| Title |
Identification of genomic enhancers through spatial integration of single-cell transcriptomics and epigenomics [ATACseq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Enhancers act as docking stations in the genome to which transcription factors bind, tightly regulating gene expression. Although single-cell technologies allow measuring chromatin accessibility or gene expression in each individual cell, exploiting both layers towards bona fide gene regulatory networks and enhancers is still a challenge. Here, we independently generate comprehensive single-cell transcriptome and epigenome atlases of the Drosophila eye-antennal disc and propose the spatial integration of single-cell RNA-seq and single-cell ATAC-seq data using a virtual latent space that mimics the spatial organization of the 2D tissue. To validate spatially predicted enhancers, we use a large collection of enhancer-reporter lines and identify ~85% of enhancers for which chromatin accessibility and enhancer activity patterns agree; while the remaining ~15% are ubiquitously accessible regions bound by the pioneer transcription factor Grainyhead, for which accessibility and activity do not correlate. Next, we infer linear and non-linear enhancer-to-target gene relationships in the virtual space, and find that genes are mostly regulated by multiple -and in some cases, redundant - enhancers. In addition, using cell-type specific enhancers learned from the scATAC-seq data, we deconvolute the cell-type specific effects of chromatin accessibility QTLs from a panel of 50 bulk ATAC-seq profiles from Drosophila inbred lines. Finally, we identify Prospero as a key transcription factor driving neuronal photoreceptor differentiation through the binding of a GGG recognition motif. In summary, we provide a comprehensive spatial characterization of gene regulation in a 2D tissue, which can be explored via SCope (http://scope.aertslab.org/#/Bravo_et_al_EyeAntennalDisc) and the UCSC Genome browser (http://genome.ucsc.edu/s/cbravo/Bravo_et_al_EyeAntennalDisc).
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| Overall design |
ATAC-seq data of the wild type Drosophila third instar larvae eye-antennal disc across a panel of 29 lines.
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| Contributor(s) |
González-Blas CB, Aerts S |
| Citation(s) |
32431014 |
| |
| Submission date |
Dec 06, 2019 |
| Last update date |
May 26, 2020 |
| Contact name |
Carmen Bravo González-Blas |
| E-mail(s) |
carmen.bravogonzalezblas@kuleuven.vib.be
|
| Organization name |
VIB-KU Leuven
|
| Department |
VIB-KU Leuven Center for Brain and Disease Research
|
| Lab |
Laboratory of Computational Biology
|
| Street address |
Herestraat 49
|
| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
| |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (29)
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| This SubSeries is part of SuperSeries: |
| GSE141590 |
Identification of genomic enhancers through spatial integration of single-cell transcriptomics and epigenomics |
|
| Relations |
| BioProject |
PRJNA593991 |
| SRA |
SRP234976 |
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