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Series GSE44420 Query DataSets for GSE44420
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
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)
GSM1084800 BACH2
GSM1084801 BCL6
GSM1084802 input
BioProject PRJNA189941
SRA SRP018803

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Supplementary file Size Download File type/resource
GSE44420_RAW.tar 305.8 Mb (http)(custom) TAR (of BED, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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