| 1998 |
ARID1A (p270) is an integral component of human SWI/SNF chromatin remodeling complexes, co-purifying with SWI/SNF subunits via antibodies raised against p300/CBP. |
Immunoprecipitation and protein purification from mammalian cells |
Molecular and cellular biology |
High |
9584200
|
| 2000 |
ARID1A (p270) contains an ARID (AT-rich interactive domain) DNA-binding motif but, unlike other ARID family members, shows no sequence-specific DNA binding preference, demonstrating that AT-rich binding is not an intrinsic property of all ARID domains. |
DNA binding assays (in vitro) with purified ARID domain |
Molecular and cellular biology |
High |
10757798
|
| 2005 |
ARID1A (p270) is specifically required for cell cycle arrest upon differentiation induction: siRNA depletion of p270 (but not the related ARID1B) causes continued DNA synthesis, failure to upregulate p21, and failure to downregulate cyclins and E2F-responsive products, demonstrating a distinct anti-proliferative role for p270-containing SWI/SNF complexes. |
siRNA knockdown, DNA synthesis assay, Western blot for p21 and cyclins in differentiation-inducible cell system |
Cancer research |
High |
16230384
|
| 2008 |
BAF250a (ARID1A) is essential for early mouse embryonic germ-layer formation (mesodermal layer) and embryonic stem cell pluripotency and self-renewal; ablation arrests development at ~E6.5, promotes primitive endoderm differentiation, and impairs cardiomyocyte and adipocyte but not neuron differentiation, correlating with altered expression of Sox2, Utf1, and Oct4. |
Mouse knockout (conditional ablation), DNA microarray, immunostaining, RNA analysis, embryoid body differentiation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18448678
|
| 2010 |
BAF250b (the ARID1B paralog) assembles with elongin C, cullin 2, and Roc1 into an E3 ubiquitin ligase that monoubiquitinates histone H2B at lysine 120 in vitro; RNAi depletion of BAF250 in human cells and mutation of Drosophila osa (its ortholog) reduce global H2B monoubiquitination, adding an enzymatic ubiquitin ligase function to SWI/SNF-A. Note: this study primarily characterizes ARID1B but also implicates BAF250/ARID1 family members in H2B ubiquitination. |
Immunopurification, in vitro ubiquitination assay, RNAi in human cells, Drosophila genetics |
Molecular and cellular biology |
Medium |
20086098
|
| 2009 |
ARID1A physically interacts with the tumor suppressor HIC1 in a BRG1-dependent manner; sequential ChIP demonstrated that HIC1 recruits ARID1A-containing SWI/SNF complexes to repress E2F1 transcription in quiescent fibroblasts; HIC1 does not interact with BRM-containing complexes, establishing specificity for ARID1A-SWI/SNF. |
Yeast two-hybrid, co-immunoprecipitation, sequential ChIP-reChIP in WI38 fibroblasts and BRG1-null SW13 cells |
Biochemical and biophysical research communications |
High |
19486893
|
| 2012 |
BAF250a (ARID1A) regulates cardiac progenitor cell differentiation in the second heart field by binding selectively to target gene promoters (Mef2c, Nkx2.5, Bmp10) and recruiting the catalytic subunit Brg1 to modulate chromatin accessibility; ablation in SHF causes right ventricular trabeculation defects, VSD, persistent truncus arteriosus, and embryonic lethality. |
Conditional mouse knockout, ChIP, DNase I digestion (chromatin accessibility), ES cell differentiation model, immunostaining |
The Journal of biological chemistry |
High |
22621927
|
| 2013 |
BAF250a physically interacts with NuRD complex subunits and cooperates with NuRD to repress cardiac gene transcription by switching chromatin between open and poised states; specific depletion of BAF250a in P19 cells causes arrhythmic contracting cardiomyocytes and modulates BRG1 occupancy at cardiac gene loci. |
Affinity purification coupled to mass spectrometry, co-immunoprecipitation, ChIP, RNA knockdown in P19 cells and embryonic heart |
Nucleic acids research |
Medium |
24335282
|
| 2014 |
Baf250a (ARID1A) maintains sinoatrial node (SAN) pacemaker cell identity by activating Tbx3 expression and, together with Tbx3 and HDAC3, coordinately repressing Nkx2.5; SAN-specific deletion causes sinus bradycardia and sick sinus disease by derepressing Nkx2.5-driven contractile cardiomyocyte gene program. |
Conditional mouse knockout (SAN-specific), transcriptomic time-series analysis, genetic epistasis |
Cell research |
High |
25145359
|
| 2015 |
BAF250a (ARID1A) regulates nucleosome occupancy at bivalent (H3K4me3/H3K27me3) promoters of key developmental genes in embryonic stem cells; acute deletion increases nucleosome occupancy at these promoters, reduces H3K27me3 and bivalent gene number, elevates Brg1 but reduces Suz12 recruitment, and disrupts differentiation timing. |
Acute conditional deletion, genome-wide nucleosome mapping (MNase-seq), histone modification ChIP-seq, gene expression analysis |
The Journal of biological chemistry |
High |
26070559
|
| 2015 |
EZH2 inhibition is synthetically lethal in ARID1A-mutated ovarian cancer cells; ARID1A and EZH2 co-occupy and regulate PIK3IP1, a direct target whose upregulation upon EZH2 inhibition suppresses PI3K-AKT signaling and mediates the synthetic lethality; EZH2 inhibition causes in vivo regression of ARID1A-mutated tumors. |
Cell viability assays, ChIP, gene expression analysis, mouse xenograft models, PI3K-AKT signaling assays |
Nature medicine |
High |
25686104
|
| 2019 |
ARID1A-mediated chromatin remodeling is required for expression of SLC7A11, a cystine transporter; ARID1A deficiency reduces basal glutathione (GSH) levels by impairing SLC7A11 expression, making ARID1A-deficient cells specifically vulnerable to GCLC inhibition through ROS-mediated apoptosis. |
ARID1A knockout cell lines, glutathione measurement, ROS assays, apoptosis assays, xenograft models, ChIP for SLC7A11 locus |
Cancer cell |
High |
30686770
|
| 2019 |
ARID1A inactivation causes defects in telomere cohesion by reducing expression of cohesin subunit STAG1; this selectively eliminates cells with gross chromosomal aberrations during mitosis, explaining why ARID1A-mutated tumors paradoxically lack copy number alterations. |
ARID1A knockout, telomere FISH, colony formation assays, ChIP for STAG1 locus, STAG1 rescue experiments, analysis of copy number alterations in cancer genomics data |
Nature communications |
High |
31492885
|
| 2019 |
ARID1A spatially partitions interphase chromosomes by interacting with condensin II; ARID1A knockout drives redistribution of condensin II preferentially to enhancers, contributes to B-compartment formation, weakens TAD borders, and increases trans interactions of small chromosomes. |
Co-immunoprecipitation (SWI/SNF–condensin II interaction), Hi-C, ChIP-seq, 3D interphase chromosome painting, ARID1A knockout cells |
Science advances |
High |
31131328
|
| 2019 |
ARID1A and PI3K pathway mutations cooperate in the endometrial epithelium: ARID1A is normally bound to promoters with open chromatin to repress EMT genes; ARID1A loss increases promoter chromatin accessibility and EMT gene expression; PI3K activation partially rescues mesenchymal phenotypes through antagonism of ARID1A target genes, resulting in partial EMT and collective invasion. |
Mouse conditional knockout (monoallelic ARID1A loss + PI3K activation), ATAC-seq, ChIP-seq, transcriptomics, invasion assays |
Nature communications |
High |
31391455
|
| 2019 |
Inflammatory IKKβ signaling phosphorylates ARID1A, leading to its degradation via β-TRCP; ARID1A loss in turn silences the enhancer of A20 deubiquitinase (a NF-κB negative regulator), unleashing CXCR2 ligand-mediated PMN-MDSC chemotaxis and creating an immunosuppressive tumor microenvironment. |
Prostate-specific conditional Arid1a knockout mouse model, co-immunoprecipitation, ChIP-seq, MDSC neutralization experiments, Western blot for IKKβ/β-TRCP/ARID1A axis |
Nature communications |
High |
36435834
|
| 2019 |
Arid1a deficiency in hepatocytes impairs fatty acid oxidation by downregulating PPARα and altering the epigenetic landscape of metabolic genes, increasing susceptibility to hepatic steatosis and insulin resistance under high-fat diet conditions. |
Hepatocyte-specific Arid1a knockout mice, glucose/insulin tolerance tests, ChIP, RNA-seq, ATAC-seq, isolated primary hepatocytes |
EBioMedicine |
High |
30879920
|
| 2020 |
ARID1A inactivation increases SWI/SNF complex targeting to genomic sites of luminal lineage-determining transcription factors (ER, FOXA1, GATA3), disrupts ER-FOXA1 chromatin interactions and ER-dependent transcription, and drives a switch from ER-dependent luminal to ER-independent basal-like cell identity, conferring resistance to ER degraders. |
CRISPR-Cas9 epigenome screen, ARID1A inactivation in cells and patient samples, ChIP-seq, ATAC-seq, gene expression profiling |
Nature genetics |
High |
31932695
|
| 2020 |
ARID1A acts as a transcriptional repressor at ER cis-regulatory elements in a FOXA1-dependent manner; deletion of ARID1A causes loss of HDAC1 binding, increased H4 lysine acetylation, and subsequent BRD4-driven transcription and cell growth, explaining sensitivity to BET inhibitors upon ARID1A loss. |
CRISPR genome-wide screen, ChIP-seq, ATAC-seq, HDAC1 co-occupancy analysis, pharmacological BET inhibition |
Nature genetics |
High |
31913353
|
| 2020 |
TRIM32 (E3 ubiquitin ligase) promotes ARID1A degradation via the ubiquitin-proteasome system in squamous cell carcinoma, while USP11 (deubiquitinase) stabilizes ARID1A; the TRIM32/USP11-ARID1A-SDC2 axis controls SCC proliferation and metastasis. |
Co-immunoprecipitation, ubiquitination assays, siRNA/shRNA knockdown, CRISPR KO, rescue experiments, in vivo tumor models |
Cell reports |
High |
31914402
|
| 2020 |
ARID1A cooperates with transcription factor CEBPα to repress UCA1 lncRNA transcription in breast cancer by regulating chromatin access at the UCA1 locus; ARID1A loss derepresses UCA1 and mediates increased cell proliferation and migration. |
siRNA knockdown, ChIP for histone modifications and ARID1A occupancy, luciferase reporter assay, rescue experiments with UCA1 |
Oncogene |
Medium |
29980791
|
| 2021 |
ARID1A loss leads to R-loop accumulation and transcription-replication conflicts; ARID1A binds ATR and TOP2A, and its loss reduces TOP2A binding at R-loop sites, implicating ARID1A in resolution of replication stress through chromatin regulation. |
ARID1A knockout cell lines, R-loop detection (S9.6 immunofluorescence/DRIP-seq), DNA fiber assays for replication dynamics, ChIP for TOP2A |
PLoS genetics |
Medium |
33826602
|
| 2021 |
ARID1A inactivation upregulates glutaminase (GLS1) because SWI/SNF normally represses GLS1; ARID1A loss shifts glucose metabolism toward glutamine-dependent TCA cycle and aspartate synthesis, creating a specific vulnerability to GLS1 inhibition. |
ARID1A knockout, metabolic flux analysis, ChIP-seq for SWI/SNF at GLS1 locus, orthotopic and patient-derived xenograft models, GLS1 inhibitor (CB-839) treatment |
Nature cancer |
High |
34085048
|
| 2021 |
ARID1A directly represses p53 pathway genes (including ATF3) in the endometrial epithelium in vivo; co-existing ARID1A and TP53 mutations promote invasive adenocarcinoma through ATF3 induction, reduced apoptosis, and TP63+ squamous differentiation. |
Genetically engineered mouse models (ARID1A/PIK3CA and TP53/PIK3CA conditional knockouts), ChIP-seq, transcriptome profiling, histopathological analysis |
PLoS genetics |
High |
34941867
|
| 2021 |
ARID1A loss activates MAPK signaling by downregulating the phosphatase DUSP4; ARID1A normally maintains histone acetylation (H3K27Ac, H3K9Ac) at DUSP4 regulatory regions; DUSP4 re-expression or MAPK pathway inhibition mitigates tumor formation in vivo. |
RNA-seq in isogenic ARID1A-null vs wild-type cells, ChIP-seq for histone marks at DUSP4 locus, DUSP4 rescue experiments, in vivo pharmacological MAPK inhibition |
Journal of biomedical science |
High |
38071325
|
| 2021 |
ARID1A physically interacts with progesterone receptor isoform PGR-A (but not PGR-B) in mouse and human endometrium; ARID1A loss reduces PgR enhancer accessibility (H3K27Ac, BRG1 signals) and decreases PR expression in endometrial epithelial neoplasia. |
Co-immunoprecipitation, proximity ligation assay, ChIP-seq for ARID1A/BRG1/H3K27Ac at PgR enhancer, immunohistochemistry in human and mouse (Pten/Arid1a KO) tissues |
Biochemical and biophysical research communications |
High |
33706098 36853791
|
| 2021 |
ARID1A loss activates mTOR signaling (increased pS6) and SOX9 nuclear expression in gastric adenocarcinoma cells and mouse gastric epithelial cells; mTOR inhibitor (RAD001) can curtail this activation, establishing an ARID1A-mTOR-SOX9 axis. |
ARID1A knockdown in GAC cell lines, CK19-Cre-Arid1a knockout mice, Western blot for pS6/SOX9, in vivo PDX models with mTOR inhibitor |
Gut |
Medium |
33785559
|
| 2021 |
Arid1a loss suppresses TGF-β/Smad4 tumor suppressor signaling in biliary cells; Kras/Arid1a double mutant mice develop cholangiocarcinoma preceded by failed engagement of TGF-β-Smad4 pathway, establishing an ARID1A-TGF-β-Smad4 axis limiting biliary epithelial oncogenic response. |
Murine conditional Kras/Arid1a knockout models with biliary and hepatocyte lineage tracing, cell culture proliferation/cell cycle assays, chromatin structure analysis, TGF-β pathway signaling readouts |
Cell reports |
Medium |
36044839
|
| 2021 |
ARID1A regulates ARID1A target gene SLC7A11 chromatin accessibility and is required for PPARα-driven fatty acid oxidation in hepatocytes, as shown by ATAC-seq and ChIP identifying reduced open chromatin at PPARα target genes upon Arid1a deletion. |
Hepatocyte-specific Arid1a KO, ATAC-seq, ChIP, RNA-seq |
EBioMedicine |
Medium |
30879920
|
| 2022 |
ARID1A recruits HDAC1 via its C-terminal DUF3518 domain to the USP9X promoter, repressing USP9X and downstream AMPK (PRKAA2) activity; ARID1A loss increases H3K9 and H3K27 acetylation at the USP9X promoter and upregulates USP9X-AMPK signaling, enabling tumor cell adaptation to glucose starvation. |
CRISPR KO, mass spectrometry for ARID1A-interacting proteins, co-IP, GST pulldown, ChIP, luciferase reporter assay |
Cellular and molecular gastroenterology and hepatology |
High |
35390516
|
| 2022 |
ARID1A loss in lung cancer increases chromatin accessibility at glycolytic gene promoters (Pgam1, Pkm, Pgk1), reduces HDAC1 recruitment and increases H4 lysine acetylation at these loci, enhancing HIF1α binding and BRD4-driven transcription of glycolytic genes and promoting metabolic reprogramming toward glycolysis. |
Genetically engineered mouse models (KP and KPA), ATAC-seq, ChIP-seq, transcriptomics, metabolic flux assays, pharmacological inhibition of glycolysis and BET |
Cancer research |
High |
34987057
|
| 2022 |
ARID1A loss in ARID1A-deficient cells leads to HDAC6-mediated EMT and enhanced invasion; HDAC6 inhibition reverses the migratory and invasive phenotype of ARID1A-knockdown endometrial cancer cells and creates apoptotic vulnerability to etoposide. |
siRNA/shRNA knockdown in endometrial cell lines and 3D primary cultures, HDAC6 inhibitor (ACY1215), in vivo mouse metastasis models |
Molecular oncology |
Medium |
35167193
|
| 2022 |
ARID1A loss induces aberrant DNA methylation (CpG island methylator phenotype, CIMP) at genomic regions with pre-existing or acquired H3K27me3; ARID1A knockout in cultured cells directly causes CIMP, indicating ARID1A normally prevents PRC2-associated DNA hypermethylation. |
ARID1A knockout in 293FT and GES1 cells, genome-wide DNA methylation analysis (EPIC array), H3K27me3 ChIP-seq |
Cancer letters |
Medium |
35131383
|
| 2023 |
ARID1A suppresses postnatal cardiomyocyte proliferation by directly binding and inhibiting YAP and TAZ, preventing their interaction with TEAD; ARID1A also promotes cardiomyocyte maturation by increasing chromatin accessibility for maturation transcription factors. Arid1a inactivation after ischemic injury enhances border zone cardiomyocyte proliferation. |
Conditional Arid1a KO in mice, genome-wide transcriptome and epigenome (ATAC-seq), co-immunoprecipitation for ARID1A-YAP/TAZ interaction, cardiac injury model |
Nature communications |
High |
37543677
|
| 2023 |
SWI/SNF (ARID1A) inactivation downregulates rate-limiting mevalonate pathway enzymes (HMGCR, HMGCS1), creating dependency on residual mevalonate pathway activity; mevalonate pathway inhibitors (statins) suppress ARID1A-mutant tumor growth and synergize with immune checkpoint blockade by promoting inflammasome-regulated pyroptosis. |
ARID1A knockout, gene expression analysis showing HMGCR/HMGCS1 downregulation, statin treatment in mouse genetic OCCC model and humanized PDX, anti-PD-L1 combination |
Cancer cell |
Medium |
36963401
|
| 2023 |
ARID1A loss in HCC represses PKM (glycolysis) expression, shifting glucose metabolism from aerobic glycolysis to TCA cycle dependence, and this creates vulnerability to copper-induced cuproptosis that directly targets the TCA cycle. |
CRISPR-Cas9 ARID1A KO, CRISPR synthetic lethality screen, transcriptomics (PKM downregulation), metabolic analysis, copper treatment in cell lines and xenografts |
Cell reports. Medicine |
Medium |
37939712
|
| 2023 |
ARID1A deficiency causes accumulation of DNA base lesions and abasic (AP) sites due to impaired base excision repair (BER); ARID1A mutations delay recruitment kinetics of long-patch BER effectors; combination of TMZ and PARP inhibitors exploits this BER defect to cause DSBs and replication stress in ARID1A-deficient cells. |
ARID1A-deficient cell lines, AP site quantification, BER protein recruitment kinetics (live cell imaging/ChIP), comet assay, in vivo xenograft models |
Cancer research |
Medium |
37306706
|
| 2024 |
ARID1A accumulates at DNA double-strand breaks (DSBs) and promotes both NHEJ and HR repair pathways; at DSBs, ARID1A recruits RAD21 and CTCF to form chromatin loops, recruits HDAC1 and RSF1 to silence transcription in active regions, controls histone mark distribution, and reduces RNAPII. ARID1A depletion enhances micronuclei accumulation and activates the cGAS-STING pathway. |
ARID1A depletion, DSB induction (ionizing radiation), immunofluorescence at DSBs, ChIP for RAD21/CTCF/HDAC1/RSF1/histone marks, RNAPII ChIP, chromatin conformation assays, cGAS-STING pathway readouts |
Nucleic acids research |
High |
38587186
|
| 2024 |
ARID1A recognizes R-loops with high affinity in an ATM-dependent manner and recruits METTL3/METTL14, which m6A-methylate R-loop RNA; this m6A modification facilitates RNase H1 recruitment to drive R-loop resolution and promote DNA end resection at DSBs. |
R-loop binding assays (in vitro and in vivo), co-immunoprecipitation of ARID1A-METTL3/14 complex, m6A modification assays, RNase H1 recruitment ChIP, cell survival upon cytotoxic agent treatment |
Cell reports |
High |
38358891
|
| 2024 |
ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors PU.1 and NF-κB at cytokine and CD40 signaling genes in germinal center B cells; absence of ARID1A tilts GC cell fate toward immature IgM+CD80-PD-L2- memory B cells. ARID1A mutation induces synthetic lethality to SMARCA2/4 inhibition. |
ARID1A conditional knockout in murine B cells, ChIP-seq for TF binding (PU.1, NF-κB), transcriptomics, flow cytometry for B cell populations, SMARCA2/4 inhibitor sensitivity assays |
Cancer cell |
High |
38458187
|
| 2024 |
ARID1A harbors a prion-like domain (PrLD) that drives liquid-liquid phase separation (LLPS), forming nuclear condensates enriched at EWS/FLI1 target enhancers in Ewing's sarcoma; ARID1A condensates induce long-range chromatin architectural changes at oncogenic target genes; disruption of ARID1A LLPS reduces proliferative and invasive abilities. |
In vitro LLPS assays, immunofluorescence of nuclear condensates, genome-wide chromatin structure profiling (Hi-ChIP/ATAC-seq), PrLD mutagenesis, Ewing's sarcoma patient specimens and cell lines |
Nature communications |
Medium |
39095374
|
| 2024 |
ARID1A is required for IRF4 expression in multiple myeloma and functionally associates with IRF4 protein on chromatin; deletion of Arid1a in activated murine B cells disrupts IRF4-dependent transcriptional networks and blocks plasma cell differentiation. |
Multi-omics (functional genomics screening, spatial proteomics, ChIP-seq), conditional Arid1a KO in murine B cells, flow cytometry for plasma cell markers, SWI/SNF inhibitor treatment |
Cancer cell |
High |
38906156
|
| 2018 |
ARID1A directly represses MVIH lncRNA transcription in HCC by binding through its ARID domain and C-terminal protein binding domain to the MVIH locus; ARID1A also upregulates CDKN1A (p21) and suppresses HCC cell proliferation and migration through inhibition of MVIH. |
Co-immunoprecipitation (ARID1A-MVIH RNA interaction), domain mapping, ChIP, siRNA knockdown, proliferation and migration assays |
Biochemical and biophysical research communications |
Low |
28716731
|
| 2021 |
ARID1A controls trophoblast cell migration and invasion by downregulating Snail transcription (reducing migration) and by binding to and destabilizing MMP-9 protein (reducing invasion); overexpression of ARID1A inhibits JEG-3 cell migration and invasion, while knockdown promotes these processes. |
ARID1A overexpression and knockdown in JEG-3 cells, Snail transcription assays, co-immunoprecipitation/co-localization of ARID1A and MMP-9, invasion/migration assays |
Reproductive sciences |
Low |
34255312
|
| 2018 |
The C-terminus of BAF250a contains an ARM-repeat fold; mutagenesis of a conserved valine (V1067G) in the ARID domain destabilizes the domain structure and abolishes DNA binding activity, demonstrating that conserved residues in the ARID are required for structural integrity and DNA interaction. |
Comparative sequence analysis, homology modeling, mutagenesis (V1067G), in vitro DNA binding affinity assay, biophysical stability measurements |
PloS one |
Medium |
30307988
|