A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020]
Transcription factors with Perturb-seq knockdown data for BCR. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = BCR upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of BCR, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr22:23,069,706–23,071,104 | 128.0 kb | Distal (>10kb) Multiome | 559 | |
| chr22:23,141,719–23,142,243 | 56.2 kb | Distal (>10kb) Multiome | 454 | |
| chr22:23,145,130–23,145,779 | 52.9 kb | Distal (>10kb) Multiome | 470 | |
| chr22:23,180,182–23,180,918 | 17.6 kb | Distal (>10kb) Multiome | 508 | |
| chr22:23,218,627–23,219,298 | 20.7 kb | Distal (>10kb) Multiome | 428 | |
| chr22:23,230,272–23,230,724 | 32.3 kb | Distal (>10kb) Multiome HiCAR | 90 | |
| chr22:23,237,087–23,237,780 | 39.1 kb | Distal (>10kb) Multiome HiCAR | 278 | |
| chr22:23,242,095–23,242,999 | 44.4 kb | Distal (>10kb) Multiome HiCAR | 214 | |
| chr22:23,243,127–23,243,375 | 44.9 kb | Distal (>10kb) Multiome | 141 | |
| chr22:23,367,107–23,367,560 | 169.2 kb | Distal (>10kb) Multiome | 18 | |
| chr22:23,402,113–23,403,060 | 204.5 kb | Distal (>10kb) Multiome | 416 |
Genomic view of the BCR locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.