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| Status |
Public on Jun 09, 2017 |
| Title |
Genome-scale Activation Screen Identifies a LncRNA Locus Regulating a Gene Neighborhood [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The mammalian genome contains thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to play critical roles in diverse cellular processes through a variety of mechanisms. While some lncRNA loci encode RNAs that act non-locally (in trans), emerging evidence indicates that many lncRNA loci act locally (in cis) to regulate expression of nearby genes—for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. To address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen targeting more than 10,000 lncRNA transcriptional start sites (TSSs) to identify noncoding loci that influence a phenotype of interest. We found 11 novel lncRNA loci that, upon recruitment of an activator, each mediate BRAF inhibitor resistance in melanoma. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation results in dosage-dependent activation of four neighboring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit to systematically discover functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function.
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| Overall design |
ChIP-seq for histone modifications in A375 cells
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| Contributor(s) |
Joung J, Zhang F |
| Citation(s) |
28792927 |
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| Submission date |
Jun 08, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Julia Joung |
| E-mail(s) |
julia@joung.science
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| Organization name |
Broad Institute
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| Street address |
75 Ames St
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE99836 |
Genome-scale Activation Screen Identifies a LncRNA Locus Regulating a Gene Neighborhood |
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| Relations |
| BioProject |
PRJNA389746 |
| SRA |
SRP108863 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99835_RAW.tar |
322.4 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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