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| Status |
Public on Nov 09, 2020 |
| Title |
An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERa action to confer to tamoxifen resistance in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Estrogen receptor alpha (ERalpha signaling pathway is essential for ERalpha positive breast cancer progression and endocrine therapy resistance. BPTF associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer are still elusive. Here, we found that higher expression of BAP18 in ERalpha positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. In addition, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERalpha is required for the recruitment of COMPASS-like core subunits to cis-regulatory element of ERalpha target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and confers to ERalpha antagonist tamoxifen resistancein ERalpha positive breast cancer. Our data suggest that BAP18 facilitates the association between ERalpha and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.
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| Overall design |
Examination of BAP18 global enrichment on chrmatin in MCF7 cell.
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| |
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| Contributor(s) |
Sun G, Wang C |
| Citation(s) |
32986841 |
| |
| Submission date |
Feb 01, 2020 |
| Last update date |
Nov 09, 2020 |
| Contact name |
Ge Sun |
| E-mail(s) |
sung@cmu.edu.cn
|
| Organization name |
China Medical University
|
| Street address |
No.77 Puhe Road, Shenyang North New Area
|
| City |
Shenyang city |
| ZIP/Postal code |
110122 |
| Country |
China |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA604328 |
| SRA |
SRP246509 |
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