TXNIP loss increases Myc genomic occupancy [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA859844 | ENA |
REPOSITORIES: ENA
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Project description:Our RNA sequencing result demonstrated that TXNIP loss increased the levels of Myc-dependent transcription. To determine whether TXNIP regulates global Myc genomic occupancy, we performed Myc ChIP-seq on parental 231 and 231:TKO cells.
2023-02-07 | GSE208412 | GEO
Project description:Our Myc ChIP sequencing result demonstrated that TXNIP loss increased Myc genomic occupancy levels. To determine whether TXNIP loss increased Myc genomic occupancy through increasing chromatin accessibility for Myc binding, we performed assay for transposase-accessible chromatin with sequencing (ATAC-seq) on parental 231 and 231:TKO cells.
2023-02-07 | GSE222672 | GEO
Project description:TXNIP loss expands Myc transcriptome
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Project description:To examine the generality of our finding where the gene expression profile of TXNIP knockout in MDA-MB-231 cells resembles of that Myc overexpression transcriptional program, our lab has generated TXNIP null HCC70 (HCC70:TKO) and MB135 (MB135:TKO) cells. We characterized the gene exrpession programs of these cells by RNA-seq.
2023-02-07 | GSE222693 | GEO
Project description:To better understand how TXNIP in the contributes to the poor prognosis of triple-negative breast cancers, our lab has generated TXNIP null MDA-MB-231 cells (231:TKO). We characterized the gene exrpession programs of these cells by RNA-seq. To determine the Myc-dependence of the transcriptional programs of 231:TKO cells, we used an siRNA RNA approach to reduce Myc levels.
2023-02-07 | GSE208415 | GEO
Project description:TXNIP loss expands Myc transcriptome [RNA-seq]
| PRJNA859857 | ENA
Project description:TXNIP loss does not increase chromatin accessibility for Myc binding.
| PRJNA922999 | ENA
Project description:The c-Myc protooncogene places a demand on glucose uptake to drive glucose-dependent biosynthetic pathways. To meet this demand, c-Myc protein (Myc henceforth) drives the expression of glucose transporters, glycolytic enzymes, and represses the expression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake. A Mychigh/TXNIPlow gene signature is clinically significant as it correlates with poor clinical prognosis in triple-negative breast cancer (TNBC) but not in other subtypes of breast cancer, suggesting a functional relationship between Myc and TXNIP. To better understand how TXNIP contributes to the aggressive behavior of TNBC, we generated TXNIP null MDA-MB-231 (231:TKO) cells for our study. We show that TXNIP loss drives a transcriptional program that resembles those driven by Myc and increases global Myc genome occupancy. TXNIP loss allows Myc to invade the promoters and enhancers of target genes that are potentially relevant to cell transformation. Together, these findings suggest that TXNIP is a broad repressor of Myc genomic binding. The increase in Myc genomic binding in the 231:TKO cells expands the Myc-dependent transcriptome we identified in parental MDA-MB-231 cells. This expansion of Myc-dependent transcription following TXNIP loss occurs without an apparent increase in Myc's intrinsic capacity to activate transcription and without increasing Myc levels. Together, our findings suggest that TXNIP loss mimics Myc overexpression, connecting Myc genomic binding and transcriptional programs to the nutrient and progrowth signals that control TXNIP expression.
| S-EPMC10058090 | biostudies-literature
Project description:Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that TXNIP is a novel BCR-ABL target gene. Suppression of TXNIP is responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, HK2 and LDHA, potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provides a novel survival pathway for the transformation of mouse BM cells. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.
2023-05-03 | GSE218451 | GEO