Arid4b physically interacts with Tfap2c in mouse embryonic stem cells

Keskin, Ezgi Gül; Huang, Jialiang; Çizmecioğlu, Nihal Terzi

doi:10.3906/biy-2010-67

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…We speculate that the stable mTOR protein levels and variable mTOR mRNA and p-mTOR levels are a mechanism for cells to respond quickly to intracellular and extracellular stimuli. Previous reports have pointed that ARID4B has a variety of regulatory roles in cell proliferation and differentiation, and the normal development and physiological process (35)(36)(37)(38)(39) , in agreement with our results. Our findings reveal another layer of Tau regulation of the mTOR-S6K1 signalling pathway, emphasising the importance of gene expression regulation in Tau-stimulated mTOR activation.…”

Section: It Is Largely Unknown Whether Tau Can Regulate the Mtor Path...supporting

confidence: 94%

“…The ARID4 subfamily has two members: ARID4A and ARID4B, also called retinoblastoma binding protein 1 (RBP1) and RBP1-like protein 1, respectively (31) . Studies have shown that ARID4B is a component of the SIN3A/histone deacetylase 1 (HDAC1) chromatin remodelling complex, and participates in the regulation of histone deacetylation and epigenetic regulation of cell physiology (33)(34)(35)(36) . Several recent studies have discovered that ARID4B plays a key role in cell growth and differentiation (36)(37)(38) , while the detailed molecular mechanism still needs to be deeply elucidated.…”

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confidence: 99%

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Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

Wang

Zhang

et al. 2021

Br J Nutr

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Taurine (Tau) has many profound physiological functions, but its role and molecular mechanism in muscle cells are still not fully understood. In this study, we investigated the role and underlying molecular mechanism of Tau on protein synthesis and proliferation of C2C12 myoblast cells. Cells were treated with Tau (0, 60, 120, 180 and 240 μM) for 24 h. Tau dose-dependently promoted protein synthesis, cell proliferation, mTOR phosphorylation, and also AT-rich interaction domain 4B (ARID4B) expression, with the best stimulatory effects at 120 μM. LY 294002 treatment showed that Tau promoted ARID4B expression in a PI3K-dependent manner. ARID4B knockdown (by siRNA transfection for 24 h) prevented Tau from stimulating protein synthesis and cell proliferation, whereas ARID4B gene activation (using the CRISPR/dCas9 technology) had stimulatory effects. ARID4B knockdown abolished Tau signaling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. ChIP-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the -4368∼-4591 bp site in the mTOR promoter, and ChIP-qPCR further detected that Tau stimulated ARID4B binding to this site. ARID4B knockdown or gene activation did not affect H3K27me3 binding to the mTOR promoter, but decreased or increased H3K27ac binding, respectively. Furthermore, ARID4B knockdown abolished the stimulation of Tau on H3K27ac binding to the mTOR promoter. In summary, these data uncover that Tau promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway, providing a deep understanding how Tau regulates anabolism in muscle cells.

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Section: It Is Largely Unknown Whether Tau Can Regulate the Mtor Path...supporting

confidence: 94%

mentioning

confidence: 99%

Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

Wang

Zhang

et al. 2021

Br J Nutr

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“…We had previously investigated TF binding motifs enriched in our ChIP results ( 15 ). No particular TF motif was found enriched in H3K4me3 or H3K27me3 ChIP peaks.…”

Section: Discussionmentioning

confidence: 99%

“…H3K4me3, H3K27Ac and H3K27me3 chromatin immunoprecipitation (ChIP)-seq experiments and subsequent data analysis were previously performed in wild-type and arid4b∆ cells on day 5 of endoderm differentiation ( 11 , 15 ). Sequencing data is available at NCBI GEO (GSE153634).…”

Section: Methodsmentioning

confidence: 99%

ARID4B loss leads to activated STAT1-dependent interferon pathway in mouse embryonic stem cells and during meso/endodermal differentiation

Terzi Çizmecioğlu

2023

J Turkish German Gynecol Assoc

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Objective: Proper deactivation of the pluripotency network and activation of a lineage-specific gene expression program are critical for mouse embryonic stem cell (mESC) differentiation. This is achieved by the coordinated action of transcription and chromatin factors. Our previous work identified ARID4B as a critical chromatin factor for mesoderm and endoderm differentiation. As part of a histone deacetylase complex, ARID4B plays a role in transcriptional suppression of its direct targets. Here, we investigated the mechanism of ARID4B function in mESC differentiation by focusing on genes and pathways that are upregulated in its absence. Material and Methods: We analyzed transcriptomic results of wild-type and arid4bΔ endoderm or mesoderm differentiated cells through integrative genomics viewer and ingenuity pathway analysis. We performed real-time quantitative polymerase chain reaction for selected genes. To understand pathway activation, we performed Western blot for candidate proteins during the time-course of differentiation. We also analyzed H3K4me3, H3K27me3 and H3K27Ac ChIP-seq results to understand changes in the chromatin environment. Results: Interferon-related genes were activated in arid4bΔ mESCs and endoderm or mesoderm directed cells. Consistent with this, higher phosphorylated STAT1 levels were found in arid4bΔ mESCs while a related phosphorylated STAT3 was unchanged. Finally, we observed a significant increase in H3K4me3 around interferon-related distal gene regulatory regions with a combination of either upregulation of H3K27Ac level or downregulation of H3K27me3 level. Conclusion: These results provide evidence that ARID4B is involved in the suppression of interferon-related genes in mESCs and during meso/endoderm differentiation through modulation, mainly of H3K4me3. This regulation might be important for successful mESC differentiation.

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Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth

Madhavan

Balakrishnan

Lakshmanachetty

et al. 2022

Clinical Cancer Research

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Purpose: Tumor relapse after radiation therapy (RT) is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMGs). RT-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of RT-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis. BCL2 has never been implicated in DMG as a RT-induced resistant mechanism. Experimental Design: We performed an integrated genomic analysis to determine genes responsible for radioresistance and a targeted drug screen to identify drugs that synergize with radiation in DMG. Effect of venetoclax on radiation-na�ve and 6Gy radiation on cells was evaluated by studying cell death, changes in BCL2 phosphorylation, reactive oxygen species (ROS), and apoptosis, as well as BCL2 association with BH3 apoptosis initiators. The efficacy of combining venetoclax with radiation was evaluated in vivo using orthotopic xenograft models. Results: BCL2 was identified as a key regulator of tumor growth after radiation in DMGs. Radiation sensitizes DMGs to venetoclax treatment independent of p53 status. Venetoclax as a monotherapy was not cytotoxic to DMG cells. Post-radiation venetoclax treatment significantly increased cell death, reduced BCL2-BIM association and augmented mitochondrial ROS leading to increased apoptosis. Combining venetoclax with RT significantly enhanced the survival of mice with DMG tumors. Conclusions: This study shows that venetoclax impedes the anti-apoptotic function of radiation-induced BCL2 in DMG leading to increased apoptosis. Results from these pre-clinical studies demonstrate the potential use of the BCL2 inhibitor, venetoclax, combined with RT for pediatric DMG.

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Arid4b physically interacts with Tfap2c in mouse embryonic stem cells

Cited by 4 publications

References 18 publications

Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

ARID4B loss leads to activated STAT1-dependent interferon pathway in mouse embryonic stem cells and during meso/endodermal differentiation

Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth

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