|
| Status |
Public on Feb 05, 2024 |
| Title |
Smarca4 (Brg1) is a haploinsufficient B-cell tumor suppressor that fine-tunes centrocyte cell fate decisions [raji_R1192C_rna] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
SMARCA4 encodes one of two mutually-exclusive ATPase subunits in the Brg/Brm associated factor (BAF) complex that is recruited by transcription factors to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ~30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperates with Myc over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of transcription factors that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family and NFκB. Loss of activity for these factors phenocopied aberrant Bcl6 activity within murine centrocytes and human BL cells. Smarca4 therefore facilitates chromatin accessibility for transcription factors that shape centrocyte trajectories, and loss of fine-control of these programs biases towards centroblast cell-fate and GC hyperplasia.
|
| |
|
| Overall design |
Gene expression profiling analysis by comparing SMARCA4 WT or R1192C mutant in a human BL cell line
|
| |
|
| Contributor(s) |
Green M |
| Citation(s) |
38458188 |
| |
| Submission date |
Feb 02, 2024 |
| Last update date |
May 07, 2024 |
| Contact name |
Michael Green |
| E-mail(s) |
mgreen5@mdanderson.org
|
| Phone |
713-745-4244
|
| Organization name |
The University of Texas MD Anderson Cancer Center
|
| Department |
Department of Lymphoma/Myeloma
|
| Street address |
7455 Fannin Street
|
| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77054 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (7)
|
|
| This SubSeries is part of SuperSeries: |
| GSE254908 |
Smarca4 (Brg1) is a haploinsufficient B-cell tumor suppressor that fine-tunes centrocyte cell fate decisions |
|
| Relations |
| BioProject |
PRJNA1072575 |
Less...
More...