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Transcriptome analysis of control and TFEB/TFE3 DKO MEFs and RAW264.7 in response to DNA Damage

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE118518 | GEO | 2018/09/30

REPOSITORIES: GEO

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Transcriptome analysis of control and TFEB/TFE3 DKO RAW264.7 in response to DNA Damage

Project description:We analyze the contribution of the transcription fators TFEB and TFE3 to the DNA Damage Response (DDR)

2018-09-30 | GSE118517 | GEO

Transcriptome analysis of control and TFEB/TFE3 DKO MEFs in response to DNA Damage

Project description:We analyze the contribution of the transcription fators TFEB and TFE3 to the DNA Damage Response (DDR)

2018-09-30 | GSE118516 | GEO

Transcriptome analysis of control and TFEB/TFE3 DKO MEFs and RAW264.7 in response to DNA Damage

Project description:Transcriptome analysis of control and TFEB/TFE3 DKO MEFs and RAW264.7 in response to DNA Damage

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Transcriptome analysis of control and TFEB/TFE3 DKO RAW264.7 in response to DNA Damage

Project description:Transcriptome analysis of control and TFEB/TFE3 DKO RAW264.7 in response to DNA Damage

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Transcriptome analysis of control and TFEB/TFE3 DKO MEFs in response to DNA Damage

Project description:Transcriptome analysis of control and TFEB/TFE3 DKO MEFs in response to DNA Damage

| PRJNA485899 | ENA

The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage.

Project description:The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress.

| S-EPMC6292694 | biostudies-literature

TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression.

Project description:To fulfill their function, pancreatic beta cells require precise nutrient-sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene expression in response to amino acid deprivation. Interestingly, ChIP-seq analysis showed binding of TFEB to super-enhancer regions that regulate insulin transcription. Conditional, beta-cell-specific, Tfeb-overexpressing, and Tfeb/Tfe3 double-KO mice showed severe alteration of insulin transcription, secretion, and glucose tolerance, indicating that TFEB and TFE3 are important physiological mediators of pancreatic function. Our findings reveal a nutrient-controlled transcriptional mechanism that regulates insulin production, thus playing a key role in glucose homeostasis at both cellular and organismal levels.

| S-EPMC10620765 | biostudies-literature

TFEB and TFE3 are novel components of the integrated stress response.

Project description:To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways.

| S-EPMC4772850 | biostudies-literature

TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response.

Project description:The MiT/TFE family of transcription factors (MITF, TFE3, and TFEB), which control transcriptional programs for autophagy and lysosome biogenesis have emerged as regulators of energy metabolism in cancer. Thus, their activation increases lysosomal catabolic function to sustain cancer cell growth and survival in stress conditions. Here, we found that TFEB depletion dramatically reduces basal expression levels of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 in various cell types. Conversely, TFEB overexpression increases p21 in a p53-dependent manner. Furthermore, induction of DNA damage using doxorubicin induces TFEB-mediated activation of p21, delays G2/M phase arrest, and promotes cell survival. Pharmacological inhibition of p21, instead, abrogates TFEB-mediated protection during the DNA damage response. Together, our findings uncover a novel and direct role of TFEB in the regulation of p21 expression in both steady-state conditions and during the induction of DNA-damage response (DDR). Our observations might open novel therapeutic strategies to promote cancer cell death by targeting the TFEB-p21 pathway in the presence of genotoxic agents.

| S-EPMC7290768 | biostudies-literature

TFEB AND TFE3 CONTROL GLUCOSE HOMEOSTASIS BY REGULATING INSULIN GENE EXPRESSION.

Project description:To fulfil their function, pancreatic beta-cells require precise nutrient sensing mechanisms that control insulin production. Transcription Factor EB (TFEB) and its homologue TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here we show that TFEB and TFE3 regulate beta-cell function and insulin expression in response to variations in nutrient availability. We found that nutrient deprivation in beta-cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta-cells depleted of both TFEB and TFE3 failed to suppress insulin gene expression in response to amino acid deprivation. Interestingly, ChIP-seq analysis showed binding of TFEB to super-enhancer regions that regulate insulin transcription. Conditional, beta-cell-specific, Tfeb-overexpressing and Tfeb/Tfe3 double-KO mice showed severe alteration of insulin transcription, secretion, and glucose tolerance, indicating that TFEB and TFE3 are important physiological mediators of pancreatic function. Our findings reveal a nutrient-controlled transcriptional mechanism that regulates insulin production, thus playing a key role in glucose homeostasis at both cellular and organismal levels.

| S-SCDT-10_15252-EMBJ_2023113928 | biostudies-other

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