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| Status |
Public on Mar 01, 2024 |
| Title |
Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma [HICHIP] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a novel p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.
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| Overall design |
In situ chromatin conformation capture followed by chromatin immunoprecipitation DNA-sequencing for the histone modification H3K27ac (H3K27ac HiChIP) in multiple myeloma cell line KMS-11 subjected to p52 knock down.
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| Contributor(s) |
Ang DA, Carter J, Deka K, Tan JH, Zhou J, Chen Q, Chng WJ, Harmston N, Li Y |
| Citation(s) |
38514625 |
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| Submission date |
Apr 21, 2023 |
| Last update date |
Apr 02, 2024 |
| Contact name |
Yinghui Li |
| E-mail(s) |
liyh@ntu.edu.sg
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| Organization name |
Nanyang Technological University
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| Department |
School of Biological Sciences
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| Lab |
05n-21
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| Street address |
60 Nanyang Drive
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| City |
Singapore |
| State/province |
Singapore |
| ZIP/Postal code |
637551 |
| Country |
Singapore |
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| Platforms (1) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE230526 |
Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma |
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| Relations |
| BioProject |
PRJNA958202 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230292_RAW.tar |
289.3 Mb |
(http)(custom) |
TAR (of BEDPE, COOL) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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