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| Status |
Public on Sep 02, 2021 |
| Title |
Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (ChIP-seq, FAIRE-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
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| Overall design |
42 or 50 bp single-end ChIP-sequencing was performed on DNA libraries generated from sorted CD19+ B cells from primary peripherial blood or lymph node biopsies of chronic lymphocytic leukemia, follicular lymphoma, and diffuse large B cell patients or donor tonsils.
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| Contributor(s) |
Andrews JM, Payton JE |
| Citation(s) |
34461601 |
| |
| Submission date |
Feb 24, 2020 |
| Last update date |
Dec 02, 2021 |
| Contact name |
Jared Andrews |
| E-mail(s) |
jared.andrews@stjude.org
|
| Organization name |
St. Jude Children's Research Hospital
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| Department |
Developmental Neurobiology
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| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (204)
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| This SubSeries is part of SuperSeries: |
| GSE145848 |
Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers |
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| Relations |
| BioProject |
PRJNA608513 |
| SRA |
SRP250582 |
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