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| Status |
Public on Apr 22, 2020 |
| Title |
ChIP-seq analysis of H3K27ac, PPARG and RXRA in human leukemia cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements (CREs), contribute to cancer pathophysiology. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage-specific CREs and mutation discovery, and uncovered 1,837 recurrently mutated CREs containing leukemia-associated non-coding variants. By enhanced CRISPR/dCas9-based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor suppressive CREs in human leukemia. Non-coding variants at KRAS and PER2 enhancers reside in nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in situ in leukemia cells. NR binding sites frequently co-localize with non-coding variants across cancer types. Hence, recurrent non-coding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.
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| |
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| Overall design |
ChIP-seq was performed to determine the chromatin occupancy of H3K27ac, PPARG and RXRA in human leukemia cell lines
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| |
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| Contributor(s) |
Li K, Zhang Y, Liu X, Liu Y, Xu J |
| Citation(s) |
32188707 |
| |
| Submission date |
Sep 18, 2019 |
| Last update date |
Jul 22, 2020 |
| Contact name |
Jian Xu |
| E-mail(s) |
Jian.Xu@stjude.org
|
| Phone |
9015955208
|
| Organization name |
St. Jude Children's Research Hospital
|
| Department |
Pathology
|
| Street address |
262 Danny Thomas Place, MS 345
|
| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE137656 |
Integrative analysis of non-coding variants in human leukemia |
|
| Relations |
| BioProject |
PRJNA566158 |
| SRA |
SRP222336 |
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