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Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling

ABSTRACT: Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling

PROVIDER: PRJNA882436 | ENA |

REPOSITORIES: ENA

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Arid1a loss potentiates pancreatic beta-cell regeneration through activation of EGF signaling

Project description:Arid1a loss potentiates pancreatic beta-cell regeneration through activation of EGF signaling

| PRJNA818989 | ENA

Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling

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

Arid1a loss potentiates pancreatic beta-cell regeneration through activation of EGF signaling

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-24 | GSE199229 | GEO

Genome-wide maps of H3K27ac ocupancy on chromatin in murine acinar cell line upon EGF treatment and Arid1a silencing

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

ChIP-seq analysis of Arid1a and C/ebpÎ± in the mouse livers

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/ebpÎ±, 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/ebpÎ± 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/ebpÎ± binds at precisely the same positions, indicating that Arid1a facilitates C/ebpÎ± binding across the genome. Perfuse and isolate primary hepatocytes from mice livers, analysis of genomic occupancy of C/ebpÎ± 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

RNA-seq transcriptonal profiling in partial hepatectomy liver tissues in Arid1a WT and liver specific KO mice.

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

Interplay of EGFR signaling and ARID1A in regulating transcriptome of celllular-plasticity genes

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

ARID1A and ARID1B loss in HCT116 cells

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

ARID1A and ARID1B loss in TOV21G cells

2017-09-29 | GSE101974 | GEO

Genome-wide occupancy profile of ARID1A in the presence and absence of epidermal growth factor stimulation in murine acinar cell line 266-6 (ChIP-seq)

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

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