Similar Datasets
Project description:Triple-negative breast cancer (TNBC), a highly aggressive subtype, currently lacks potent targeted therapies. ARID1B, a key SWI/SNF chromatin remodeling complex subunit, is linked to high-grade malignancies and poorer prognosis, making it a potential biomarker and therapeutic target. However, its function and regulation remain unclear. Here, we found that uncontrolled accumulation of ARID1B and its nuclear import promoted oncogenesis and drug resistance. ARID1B negatively regulates ARID1A, impairing SWI/SNF-mediated tumor suppression and enhancing tumor survival. Using protein complex purification and mass spectrometry, we identified KPNA2-KPNB1-RANBP2 as a critical protein cascade that facilitates ARID1B nuclear import. Replacing R1518, H1519, and D1522 residues on ARID1B with T1518, G1519, and G1522 attenuated the ARID1B-KPNA2 interaction, preventing recruitment of ARID1B to the nuclear pore complex. Pharmacological inhibition of KPNB1 suppressed ARID1B translocation, thereby limiting its nuclear levels. Our RNA-seq and ChIP-seq analyses indicated that KPNB1 inhibition also mimicked the effects of the SWI/SNF inhibitor on chromatin accessibility and gene expression, likely due to the reduced nuclear levels of ARID1B. In TNBC mouse models, ARID1B knockout significantly reduced tumor growth and enhanced PARP inhibitor efficacy. Collectively, our findings reveal that disrupting ARID1B nuclear translocation could be a new therapeutic strategy for TNBC.
2026-01-20 | GSE296382 | GEO
Project description:We transduced either an empty vector or ARID1B cDNA in IMR90 cells. Cells were selected with puromycin and 6 days after the infection we collected the RNA. ARID1B is a member of the SWI/SNF chromatin-remodeling complex. Our previous experiments showed that knockdown of ARID1B allows cells to bypass cellular senescence. By performing RNA-seq we have shown that ARID1B expression can induce a set of genes involved in the senescence response.
2016-11-12 | GSE75291 | GEO
Project description:Estrogen Receptor alpha (ERα) is a key driver of most breast cancers, and it is the target of endocrine therapies used in the clinic to treat women with ERα positive (ER+) breast cancer. The two methods ChIP-seq (chromatin immunoprecipitation coupled with deep sequencing) and RIME (Rapid Immunoprecipitation of Endogenous Proteins) have greatly improved our understanding of ERα function during breast cancer progression and in response to anti-estrogens. A critical component of both ChIP-seq and RIME protocols is the antibody that is used to pull down the bait protein. To date, most of the ChIP-seq and RIME experiments for the study of ERα have been performed using the sc-543 antibody from Santa Cruz Biotechnology. However, this antibody has been discontinued, thereby severely impacting the study of ERα in normal physiology as well as diseases such as breast cancer and ovarian cancer. Here, we compare the sc-543 antibody with other commercially available antibodies, and we show that 06-935 (EMD Millipore) and ab3575 (Abcam) antibodies can successfully replace the sc-543 antibody for ChIP-seq and RIME experiments.
2019-03-21 | PXD012930 | Pride
Project description:To identify ARID1B associated genes in development of neural progenitor , we carried out RNA-seq gene expression profiling analysis in primarily cultured neurospheres from ARID1B haploinsufficient and control mice. 3 biological independent sample from ARID1B hi (hGAFPCre+;ARID1B flox/+) mice were compared with 2 independent litermate control (hGAFPCre+; ARID1B +/+) samples.
2021-01-07 | GSE143171 | GEO
Project description:Triple-negative breast cancer (TNBC), a highly aggressive subtype, currently lacks potent targeted therapies. ARID1B, a key SWI/SNF chromatin remodeling complex subunit, is linked to high-grade malignancies and poorer prognosis, making it a potential biomarker and therapeutic target. However, its function and regulation remain unclear. Here, we found that uncontrolled accumulation of ARID1B and its nuclear import promoted oncogenesis and drug resistance. ARID1B negatively regulates ARID1A, impairing SWI/SNF-mediated tumor suppression and enhancing tumor survival. Using protein complex purification and mass spectrometry, we identified KPNA2-KPNB1-RANBP2 as a critical protein cascade that facilitates ARID1B nuclear import. Replacing R1518, H1519, and D1522 residues on ARID1B with T1518, G1519, and G1522 attenuated the ARID1B-KPNA2 interaction, preventing recruitment of ARID1B to the nuclear pore complex. Pharmacological inhibition of KPNB1 suppressed ARID1B translocation, thereby limiting its nuclear levels. Our RNA-seq and ATAC-seq analyses indicated that KPNB1 inhibition also mimicked the effects of the SWI/SNF inhibitor on chromatin accessibility and gene expression, likely due to the reduced nuclear levels of ARID1B. In TNBC mouse models, ARID1B knockout significantly reduced tumor growth and enhanced PARP inhibitor efficacy. Collectively, our findings reveal that disrupting ARID1B nuclear translocation could be a new therapeutic strategy for TNBC.
2026-01-20 | GSE274400 | GEO
Project description:The BAF complex modulates chromatin accessibility. Specific BAF configurations have functional consequences, and subunit switches are essential for cell differentiation. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause a neurodevelopmental disorder spectrum, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we reprogrammed ARID1B+/- Coffin-Siris patient-derived skin fibroblasts into iPSCs, and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF), including SMARCA4, and nine additional subunits. ARID1B-BAF acts as a gate-keeper, ensuring exit from pluripotency and lineage commitment, by attenuating NANOG, SOX2 and the thousands of enhancers directly regulated by these two pluripotency factors at the iPSC stage. In iPSCs, these enhancers are maintained active by an ARID1A-containing BAF. At the onset of differentiation, cells transition from ARID1A-BAF to ARID1B-BAF, eliciting attenuation of the NANOG/SOX2 networks, and triggering pluripotency exit. Coffin-Siris patient cells fail to perform the ARID1A/ARID1B switch, and maintain ARID1A-BAF at pluripotency enhancers throughout all stages of CNCC formation. This leads to a persistent and aberrant SOX2 and NANOG activity, which impairs CNCC formation. In fact, despite showing the typical neural crest signature (TFAP2A+, SOX9+), the ARID1B-haploinsufficient CNCCs are also NANOG-positive, in stark contrast with the ARID1B-wt CNCCs, which are NANOG-negative. These findings suggest a connection between ARID1B mutations, neuroectoderm formation, and a pathogenic mechanism for Coffin-Siris syndrome.
2021-10-12 | PXD028557 | Pride
Project description:Triple-negative breast cancer (TNBC), a highly aggressive subtype, currently lacks potent targeted therapies. ARID1B, a key SWI/SNF chromatin remodeling complex subunit, is linked to high-grade malignancies and poorer prognosis, making it a potential biomarker and therapeutic target. However, its function and regulation remain unclear. Here, we found that uncontrolled accumulation of ARID1B and its nuclear import promoted oncogenesis and drug resistance. ARID1B negatively regulates ARID1A, impairing SWI/SNF-mediated tumor suppression and enhancing tumor survival. Using protein complex purification and mass spectrometry, we identified KPNA2-KPNB1-RANBP2 as a critical protein cascade that facilitates ARID1B nuclear import. Replacing R1518, H1519, and D1522 residues on ARID1B with T1518, G1519, and G1522 attenuated the ARID1B-KPNA2 interaction, preventing recruitment of ARID1B to the nuclear pore complex. Pharmacological inhibition of KPNB1 suppressed ARID1B translocation, thereby limiting its nuclear levels. Our RNA-seq and ATAC-seq analyses indicated that KPNB1 inhibition also mimicked the effects of the SWI/SNF inhibitor on chromatin accessibility and gene expression, likely due to the reduced nuclear levels of ARID1B. In TNBC mouse models, ARID1B knockout significantly reduced tumor growth and enhanced PARP inhibitor efficacy. Collectively, our findings reveal that disrupting ARID1B nuclear translocation could be a new therapeutic strategy for TNBC.
2026-01-20 | GSE274401 | GEO
Project description:Triple-negative breast cancer (TNBC), a highly aggressive subtype, currently lacks potent targeted therapies. ARID1B, a key SWI/SNF chromatin remodeling complex subunit, is linked to high-grade malignancies and poorer prognosis, making it a potential biomarker and therapeutic target. However, its function and regulation remain unclear. Here, we found that uncontrolled accumulation of ARID1B and its nuclear import promoted oncogenesis and drug resistance. ARID1B negatively regulates ARID1A, impairing SWI/SNF-mediated tumor suppression and enhancing tumor survival. Using protein complex purification and mass spectrometry, we identified KPNA2-KPNB1-RANBP2 as a critical protein cascade that facilitates ARID1B nuclear import. Replacing R1518, H1519, and D1522 residues on ARID1B with T1518, G1519, and G1522 attenuated the ARID1B-KPNA2 interaction, preventing recruitment of ARID1B to the nuclear pore complex. Pharmacological inhibition of KPNB1 suppressed ARID1B translocation, thereby limiting its nuclear levels. Our RNA-seq and ATAC-seq analyses indicated that KPNB1 inhibition also mimicked the effects of the SWI/SNF inhibitor on chromatin accessibility and gene expression, likely due to the reduced nuclear levels of ARID1B. In TNBC mouse models, ARID1B knockout significantly reduced tumor growth and enhanced PARP inhibitor efficacy. Collectively, our findings reveal that disrupting ARID1B nuclear translocation could be a new therapeutic strategy for TNBC.
2026-01-20 | GSE296383 | GEO