SMARCA4 reads PRMT1-mediated H4R3me2a to promote colorectal cancer progression I
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PROVIDER: PRJNA599181 | ENA |
REPOSITORIES: ENA
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Project description:To further investigate the functional associations between PRMT1 and SMARCA4 and explore the biological significance of these interactions, we conducted expression profiling on the Agilent SurePrint G3 Human Gene Expression v3 (8*60K,Design ID:072363) using knockdown of PRMT1 or SMARCA4’s RNA in HCT116 cells.
2020-01-07 | GSE143199 | GEO
Project description:To further investigate the functional associations between PRMT1 and SMARCA4 and explore the biological significance of these interactions, we conducted expression profiling on the Agilent SurePrint G3 Human Gene Expression v3 (8*60K,Design ID:072363) using knockdown of PRMT1 or SMARCA4’s RNA in HCT116 cells.
2020-01-07 | GSE143198 | GEO
Project description:SMARCA4 reads PRMT1-mediated H4R3me2a to promote colorectal cancer progression II
| PRJNA599180 | ENA
Project description:BackgroundAberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood.MethodsIn this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression.ResultsWe show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-ApcMin/+ CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC.ConclusionPRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
| S-EPMC8048298 | biostudies-literature
Project description: Not available
| S-EPMC8491380 | biostudies-literature
Project description:Colorectal cancer (CRC) arises from multi-step accumulation of genetic and epigenetic mutations that deregulate intestinal homeostasis leading to neoplastic transformation and metastases. Constitutive activation of WNT signaling is considered the initial driver oncogenic event to which CRCs remain addicted, also in their most aggressive metastatic forms. WNT activation provokes an aberrant signaling that converges into the nucleus where transcription and chromatin-remodeling factors cooperate to regulate cell identity. This leads to deregulated proliferation, block of differentiation and evasion from cell death pathways. We found that the protein arginine methyltransferase 1 (PRMT1) is synthetic lethal with WNT oncogenic activation in both genetically-defined mouse models and patient-derived metastatic CRC organoids. WNT activation regulates the subcellular localization of PRMT1, inducing its complete nuclear translocation. This makes CRCs specifically dependent on PRMT1 enzymatic activity to sustain WNT-dependent proliferation regardless of the mutational landscape carried by distinct patients. Together these data uncover a new molecular crosstalk between WNT activation and PRMT1 activity and place PRMT1 inhibition as a potential strategy to counteract CRC addiction to WNT oncogenic activation.
2024-07-01 | GSE179305 | GEO
Project description:ACTB is a cytoskeletal protein involved in intracellular trafficking. In recent years, it has become evident that, in addition to its established roles in these compartments, ACTB also participates in the regulation of transcription. However, the molecular mechanisms underlying this function remain poorly understood. The methyltransferase SETD3 has previously been shown to methylate ACTB at H73, thereby regulating ACTB polymerization and smooth muscle contraction. Here, we show that the genomic distribution of ACTB is SETD3-dependent and that this regulation modulates the transcription of genes involved in cell adhesion and mRNA translation in colorectal cancer cells. Proteomic analyses reveal that ACTB and SETD3 interact with multiple large protein complexes, including complexes associated with transcriptional regulation. Specifically, we demonstrate that SETD3-mediated ACTB methylation is required for the co-localization of SMARCA4, a subunit of the SWI/SNF BAF complex, at specific genomic loci. Genomic analyses further show that this co-localization enables the coordinated occupancy of SMARCA4 and H73-methylated ACTB at genes involved in cell adhesion and mRNA translation. Finally, phenotypic assays confirm these regulatory effects. Together, these findings uncover a new mechanistic layer of selective transcriptional regulation mediated by an ACTB–SETD3–SMARCA4 axis in colorectal cancer cells.
2026-01-29 | GSE308376 | GEO
Project description:ACTB is a cytoskeletal protein involved in intracellular trafficking. In recent years, it has become evident that, in addition to its established roles in these compartments, ACTB also participates in the regulation of transcription. However, the molecular mechanisms underlying this function remain poorly understood. The methyltransferase SETD3 has previously been shown to methylate ACTB at H73, thereby regulating ACTB polymerization and smooth muscle contraction. Here, we show that the genomic distribution of ACTB is SETD3-dependent and that this regulation modulates the transcription of genes involved in cell adhesion and mRNA translation in colorectal cancer cells. Proteomic analyses reveal that ACTB and SETD3 interact with multiple large protein complexes, including complexes associated with transcriptional regulation. Specifically, we demonstrate that SETD3-mediated ACTB methylation is required for the co-localization of SMARCA4, a subunit of the SWI/SNF BAF complex, at specific genomic loci. Genomic analyses further show that this co-localization enables the coordinated occupancy of SMARCA4 and H73-methylated ACTB at genes involved in cell adhesion and mRNA translation. Finally, phenotypic assays confirm these regulatory effects. Together, these findings uncover a new mechanistic layer of selective transcriptional regulation mediated by an ACTB–SETD3–SMARCA4 axis in colorectal cancer cells.
2026-01-29 | GSE308375 | GEO
Project description:ACTB methylation regulates SMARCA4 genomic occupancy to promote translation and reduce adhesion in colorectal cancer cells
| PRJNA1330305 | ENA
Project description:ACTB methylation regulates SMARCA4 genomic occupancy to promote translation and reduce adhesion in colorectal cancer cells
| PRJNA1330304 | ENA