Transcriptional elongation machinery controls vulnerability of breast cancer cells to PRC2 inhibitors
Xu, W.; Chan, N. T.; Liu, P.; Huang, J.; Wang, Y.; Ong, I. M.; Li, L.
Show abstract
CTR9 is the scaffold subunit in Paf1c, a multifunctional complex regulating multiple steps of RNA Pol II-mediated transcription. Using inducible and stable CTR9 knockdown breast cancer cell lines, we discovered that the expression of a subset of KDMs, including KDM6A and Jarid2, is strictly controlled by CTR9. Global analyses of histone modifications revealed a significant increase of H3K27me3 upon loss of CTR9. Loss of CTR9 results in a decrease of H3K4me3 and H3K36me3 in gene bodies, and elevated levels and genome-wide expansion of H3K27me3. Mechanistically, CTR9 depletion triggers a PRC2 subtype switching from PRC2.2 to PRC2.1. As a consequence, CTR9 depletion generates vulnerability that renders breast cancer cells hypersensitive to PRC2 inhibitors. Our findings that CTR9 demarcates PRC2-mediated H3K27me3 levels and genomic distribution, provide a unique mechanism of transition from transcriptionally active to repressive chromatin states and sheds light on the biological functions of CTR9 in development and cancer.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Co-regulation and functional cooperativity of FOXM1 and RHNO1 bidirectional genes in ovarian cancer 96%
- Oncogenic PKA signaling stabilizes MYC oncoproteins via an aurora kinase A-dependent mechanism 96%
- Loss function of tumor suppressor FRMD8 confers resistance to tamoxifen therapy via a dual mechanism 96%
Similar papers in this journal
- CRISPR/Cas9 screen reveals a role of purine synthesis for estrogen receptor α activity and tamoxifen resistance of breast cancer cells 95%
- MeCP2 Interacts with the Super Elongation Complex to Regulate Transcription 95%
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- SETDB1 Fuels the Lung Cancer Phenotype by Modulating Epigenome, 3D Genome Organization and Chromatin Mechanical Properties 96%
- Distinct structural and functional heterochromatin partitioning of lamin B1 and B2 revealed using genome-wide Nicking Enzyme Epitope targeted DNA sequencing. 96%
- Proteome-wide microarray-based screening of PAR-binding proteins 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.