 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 27, 2013 |
| Title |
BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The B cell-specific BACH2 transcription factor is required for affinity maturation of mature B cells. Here, we show that Bach2 mediates negative selection at the pre-B cell receptor checkpoint and functions as a critical safeguard against leukemogenesis. Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin VH-DJH gene segments, and thus lack pre-B cell receptor expression. Upon productive VH-DJH gene rearrangement, pre-B cell receptor signaling ends negative selection through BCL6-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, Bach2-mediated checkpoint control is frequently compromised and low levels of Bach2 expression represent a strong independent predictor of poor clinical outcome. Bach2+/+ pre-B cells resist leukemic transformation by Myc through Bach2-dependent upregulation of p53. Upon transformation with Myc, Bach2-/- pre-B cells fail to upregulate p53, form large colonies and initiate fatal leukemia in transplant recipient mice. ChIP-seq and gene expression analyses revealed that BACH2 competes with BCL6 for promoter binding and reverses BCL6-mediated repression of p53 and multiple other checkpoint control genes. These findings identify Bach2 as a key activator of p53 in pre-B cells, which is critical to maintain stringency of the pre-B cell receptor checkpoint and an important barrier against leukemic transformation.
|
| |
|
| Overall design |
ChIP-seq using BACH2 and BCL6 antibodies in OCI-Ly7 cells
|
| |
|
| Contributor(s) |
Huang C, Geng H, Melnick A |
| Citation(s) |
24277074, 23852341 |
| Submission date |
Feb 20, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Huimin Geng |
| E-mail(s) |
huimin.geng@ucsf.edu
|
| Organization name |
UCSF
|
| Department |
Department of Laboratory Medicine
|
| Street address |
513 Parnassus Ave., MSB S-1480
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
|
| Samples (3) |
|
| Relations |
| BioProject |
PRJNA189941 |
| SRA |
SRP018803 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44420_RAW.tar |
305.8 Mb |
(http)(custom) |
TAR (of BED, BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
