Arid1a loss potentiates pancreatic beta-cell regeneration through activation of EGF signaling
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ABSTRACT:
PROVIDER: PRJNA818989 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The dynamic regulation of β-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of β-cell regeneration. Arid1a is highly expressed in quiescent β-cells but is physiologically suppressed when β-cells proliferate during pregnancy or after pancreas resection. Whole body Arid1a knockout mice are protected against streptozotocin induced diabetes. Cell-type and temporally specific genetic dissection show that β-cell specific Arid1a deletion can potentiate β-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets reveal increased Neuregulin-ERBB-NR4A signaling. Chemical inhibition of ERBB or NR4A1 was able to block increased regeneration associated with Arid1a loss. mSWI/SNF complex activity is a barrier to β-cell regeneration in physiologic and disease states.
2022-09-20 | GSE213780 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-24 | GSE199229 | GEO
Project description:Chromatin Immunoprecipitation-based sequencing (ChIP-seq) of H3K27ac was conduced in murine Kras-mutant acinar cell line 266-6 in the context of Arid1a-knockdown and/or EGF treatment. We found EGFR signaling activation as well as Arid1a silencing leads to additional increase of H3K27ac level genome-widely. And the maximal H3K27ac was achieved by the combined- EGF treatment and Arid1a knockdown.
2023-05-31 | GSE166331 | GEO
Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver and other adult tissues results in improved organ regeneration. Within SWI/SNF complexes, Arid1a physically interacts with C/ebpα, a hepatocyte transcription factor that drives maturation and limits proliferation. Genome-wide analysis showed that loss of Arid1a reduces the recruitment and activity of C/ebpα on target promoters, resulting in expression programs that favor regeneration and cellular fitness during injury. Arid1a binding is enriched in promoters near transcriptional start sites (TSSs), and C/ebpα binds at precisely the same positions, indicating that Arid1a facilitates C/ebpα binding across the genome. Perfuse and isolate primary hepatocytes from mice livers, analysis of genomic occupancy of C/ebpα and H3K4me2 in hepatocytes from Arid1a WT and Arid1a liver specific KO mice by ChIP-seq. Analysis of genomic occupancy of Arid1a in the hepatocytes from V5-Arid1a transgenic mouse by ChIP-seq.
2016-03-30 | E-GEOD-65167 | biostudies-arrayexpress
Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver results in improved liver regeneration after partial hepatectomy.Genome-wide analysis showed that after hepatectomy,loss of Arid1a reduces the recruitment and activity of E2F4 on target promoters, resulting in expression programs that favor regeneration during injury.RNAseq shows transcriptional profiling in WT and Arid1a LKO livers pre- and post-hepatectomy, which confirmed the E2F4 target genes and cell cycle genes were upregulated after hepatectomy. After partial hepatectomy, liver transcriptional profiling in WT and Arid1a liver specific KO mice were generated by RNA-seq analysis.
2016-03-30 | E-GEOD-76926 | biostudies-arrayexpress
Project description:mRNA expression profiles of Arid1a-wildtype and Arid1a-knockdown murine 266-6 cells were generated, in the presence or absence of EGF. We found that EGFR signaling activation and Arid1a loss cooperatively upregulate a subset of genes which are involved in cellular palsticity regulation.
2023-05-31 | GSE166329 | GEO
Project description:ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation. Changes in accessibility are predictive of changes in expression and correlate with loss of H3K4me and H3K27ac marks, nucleosome spacing, and transcription factor binding, particularly at growth pathway genes including MET. We find that ARID1B knockdown in ARID1A mutant ovarian cancer cells causes similar loss of enhancer architecture, suggesting that this is a conserved function underlying the synthetic lethality between ARID1A and ARID1B.
2017-09-29 | GSE101974 | GEO
Project description:ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation. Changes in accessibility are predictive of changes in expression and correlate with loss of H3K4me and H3K27ac marks, nucleosome spacing, and transcription factor binding, particularly at growth pathway genes including MET. We find that ARID1B knockdown in ARID1A mutant ovarian cancer cells causes similar loss of enhancer architecture, suggesting that this is a conserved function underlying the synthetic lethality between ARID1A and ARID1B.
2017-09-29 | GSE101966 | GEO
Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver and other adult tissues results in improved organ regeneration. Within SWI/SNF complexes, Arid1a physically interacts with C/ebpα, a hepatocyte transcription factor that drives maturation and limits proliferation. Genome-wide analysis showed that loss of Arid1a reduces the recruitment and activity of C/ebpα on target promoters, resulting in expression programs that favor regeneration and cellular fitness during injury. Arid1a binding is enriched in promoters near transcriptional start sites (TSSs), and C/ebpα binds at precisely the same positions, indicating that Arid1a facilitates C/ebpα binding across the genome.
2016-03-30 | GSE65167 | GEO
Project description:We identified the genome binding profile of SWI/SNF complex component ARID1A in pancreatic acinar cells. By comparing the genomic occupancy profiles, we found that EGF strikingly diminished ARID1A genome-wide affinity to the chromatin.
2023-05-31 | GSE166330 | GEO