TANK binding kinase 1 induces transcription factor BACH1 to regulate iron metabolism in pancreatic cancer cells
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ABSTRACT:
PROVIDER: PRJNA830855 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18888704.fastq.gz | Fastqsanger.gz | |||
| SRR18888705.fastq.gz | Fastqsanger.gz | |||
| SRR18888706.fastq.gz | Fastqsanger.gz | |||
| SRR18888707.fastq.gz | Fastqsanger.gz |
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Project description:BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species and promotes metastasis of various cancers including pancreatic ductal adenocarcinoma (PDAC). Knockdown of Tank binding kinase 1 (TBK1) led to reductions of BACH1 mRNA and protein amounts in AsPC-1 human PDAC cells. Gene expression analysis of PDAC cells with knockdown of TBK1 or BACH1 suggested the involvement of TBK1 and BACH1 in the regulation of iron homeostasis. Ferritin was increased upon BACH1 knockdown in AsPC-1 cells. Cytometry analysis showed that AsPC-1 cells with BACH1 knockout or knockdown contained lower labile iron than control cells, suggesting that BACH1 increased labile iron by repressing the expression of ferritin genes.
2022-08-31 | GSE201307 | GEO
Project description:Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.
2016-12-14 | GSE78955 | GEO
Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach1 regulates by heme. Here we investigated the relationship between heme-regulated Bach1 and bone marrow derived macrophage. We found that Bach1 KO macrophage showed that up-regulated genes were the process that iron-heme homeostasis and maintenance related gene compared with WT. Our results suggest that Bach1 expression is important to the heme homeostasis and maintenance in the bone marrow derived macrophage.
2019-03-30 | GSE79717 | GEO
Project description:Exacerbated oxidative stress response is known to regulate cellular necrosis by triggering lipid peroxidation in an iron-dependent manner and this form of necrotic death has been implicated in Mycobacterium tuberculosis (Mtb) infection and disease. Here we examined the role of Bach1, a transcription factor that represses a major set of antioxidant genes, in regulating host resistance to Mtb. In response to Mtb infection in vitro and in vivo, ablation of Bach1 increased the levels of glutathione as well as enhanced the expression of Gpx4, an enzyme that regulates lipid peroxidation. Consistent with these observations, Bach1-/- macrophages exhibited increased resistance to Mtb-induced necrosis and infected Bach1-deficient mice displayed a striking reduction in bacterial loads as well as pulmonary necrosis and lipid peroxidation reflected in their enhanced survival. In addition, single-cell RNAseq analysis of the lungs of Mtb-infected Bach1-/- mice revealed an enrichment of a gene signature associated with protection against ferroptotic cell death. Finally, deletion of Bach1 in B6.Sst1S mice, an inbred strain that recapitulates the necrotic lung pathology seen in human TB, enhanced host resistance to Mtb while significantly reducing tissue necrosis. These findings identify Bach1 as an important regulator of cellular and tissue necrosis in Mtb infection and as such a potential target for host-direct therapy of tuberculosis.
2023-06-30 | GSE236053 | GEO
Project description:BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we combined chromatin immunoprecipitation-sequencing (ChIP-seq) analysis of BACH1 target genes in HEK 293 cells with knock-down of BACH1 using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. The 59 BACH1 target genes identified by ChIP-seq were found highly enriched in genes showing expression changes after BACH1 knock-down, demonstrating the impact of BACH1 repression on transcription. In addition to known and new BACH1 targets involved in heme degradation (HMOX1, FTL, FTH1, ME1, SLC48A1) and redox regulation (GCLC, GCLM, SLC7A11), we also discovered BACH1 target genes effecting cell cycle and apoptosis pathways (ITPR2, CALM1, SQSTM1, TFE3, EWSR1, CDK6, BCL2L11, MAFG) as well as subcellular transport processes (CLSTN1, PSAP, MAPT, vault RNA). The newly identified impact of BACH1 on genes involved in neurodegenerative processes and proliferation provides an interesting basis for future dissection of BACH1-mediated gene repression in neurodegeneration and virus-induced cancerogenesis. Examination of BACH1 binding in HEK 293T cells by chromatin immunoprecipitation-sequencing (CHIP-seq) with input DNA as control.
2011-05-13 | E-GEOD-28051 | biostudies-arrayexpress
Project description:The transcription factor BACH1 is a transcriptional repressor with a central role regulating oxidative stress and anti-inflammatory pathways, emerging as a promising therapeutic target for multiple conditions, including neurodegenerative disorders, ischemia-reperfusion injuries, sickle cell disease and cancer. In the field of cancer BACH1 has gained significant attention, with BACH1 overexpression correlating with poor prognosis and metastasis across various cancer types; however, despite this increasing relevance of BACH1, no universal pro-metastatic mechanism or transcriptional signature for BACH1 has been identified which is a major limitation for this growing field. To fill this gap, in this study we performed RNA-Seq coupled with ChIP-Seq in BACH1 proficient and deficient lung cancer cells and identified a set of common BACH1 directly regulated genes, which we thoroughly validated in a large panel of cancer cells. This novel lung cancer BACH1 transcriptional signature is highly sensitive and specific to BACH1 perturbations (both genetic and pharmacological) and does not respond to NRF2 modulation, underscoring its specificity. This signature not only represents a robust surrogate for BACH1 activity, but we also provide evidence of its potential value as a tool to i) identify novel BACH1 inhibitors; and ii) provide insights into BACH1’s pro-metastatic role.
2025-08-06 | GSE288626 | GEO
Project description:Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. While ferroptosis has been identified as a mechanism for suppressing cancer, its overall physiological significance remains poorly understood. Recent studies have revealed that labile iron and lipid peroxides are released from ferroptotic cells, leading to the propagation of ferroptosis through lipid peroxidation. However, other specific effects of secreted factors derived from ferroptotic cells remain unclear. We constructed a model cell system capable of inducing ferroptosis by re-expressing the transcription factor BACH1, a potent inducer of ferroptosis, in immortalized mouse embryonic fibroblasts (iMEFs). We investigated the impact of the secreted factors from ferroptotic cells with the iMEFs. As a result, we observed that the administration of supernatant media from ferroptotic iMEFs activated proliferation of hepatoma cells and suppressed cellular senescence-like features. This suggested that ferroptotic MEFs secrete anti-senescent substances. Transcriptome analysis of ferroptotic MEFs revealed an increase in the secretion of longevity factor FGF21 in a BACH1-dependent manner. Furthermore, the anti-senescent effects of the supernatant media from these ferroptotic cells were canceled by the knockout of Fgf21. Totally, it is suggested that BACH1 promotes ferroptosis in fibroblasts and contributes to the suppression of cellular senescence in neighboring cells by inducing FGF21 secretion from fibroblasts. It was also discovered that BACH1 not only activates indirectly the transcription of FGF21 by enhancing ferroptotic stress but also increases FGF21 protein level by suppressing the selective autophagic degradation of FGF21 through the transcriptional repression for Sqstm1 and Lamp2a. This represents a dual mechanism of FGF21 upregulation mediated by BACH1, suggesting that BACH1 is a potent inducer of FGF21 expression. It was also found that the BACH1-ferroptosis-FGF21 axis can suppress obesity of mice under high fat diet or short lifespan of progeria mice, closely associated phenotypes with aging. The inhibition of these aging-related phenotypes is considered to be a novel physiological significance of ferroptosis, and BACH1 is considered to function as a longevity gene by promoting ferroptotsis and subsequent FGF21 expression.
2024-06-11 | GSE238147 | GEO
Project description:The transcription factor BACH1 is a transcriptional repressor with a central role regulating oxidative stress and anti-inflammatory pathways, emerging as a promising therapeutic target for multiple conditions, including neurodegenerative disorders, ischemia-reperfusion injuries, sickle cell disease and cancer. In the field of cancer BACH1 has gained significant attention, with BACH1 overexpression correlating with poor prognosis and metastasis across various cancer types; however, despite this increasing relevance of BACH1, no universal pro-metastatic mechanism or transcriptional signature for BACH1 has been identified which is a major limitation for this growing field. To fill this gap, in this study we performed RNA-Seq coupled with ChIP-Seq in BACH1 proficient and deficient lung cancer cells and identified a set of common BACH1 directly regulated genes, which we thoroughly validated in a large panel of cancer cells. This novel lung cancer BACH1 transcriptional signature is highly sensitive and specific to BACH1 perturbations (both genetic and pharmacological) and does not respond to NRF2 modulation, underscoring its specificity. This signature not only represents a robust surrogate for BACH1 activity, but we also provide evidence of its potential value as a tool to i) identify novel BACH1 inhibitors; and ii) provide insights into BACH1’s pro-metastatic role.
2025-08-06 | GSE288627 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE28050: Expression data from knockdown of BACH1 in HEK 293T cells GSE28051: Genome-wide map of BACH1 binding in HEK293T cells Refer to individual Series
2011-05-12 | E-GEOD-28053 | biostudies-arrayexpress