MYC-MNT-MAX
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB23604 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2203801.fastq.gz | Fastqsanger.gz | |||
| ERR2203802.fastq.gz | Fastqsanger.gz | |||
| ERR2203803.fastq.gz | Fastqsanger.gz | |||
| ERR2203804.fastq.gz | Fastqsanger.gz | |||
| ERR2203805.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The goal of this study was to genomic occupancy of MAX, MNT, MYC and E2F1 in B cells in the presence and absence of transcription factor MAX Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell specific deletion of Max has a modest effect on B-cell development but completely abrogates E -Myc driven lymphomagenesis. While Max loss only affects a few hundred genes in normal B cells, it leads to the global downregulation of Myc-activated genes in premalignant E -Myc cells. We show that the balance between MYC-MAX and MNT-MAX interactions in B cells shifts in pre-malignant B cells towards a MYC driven transcriptional program. Moreover, we find that MAX loss leads to a significant reduction in MYC protein levels and downregulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC-MAX dimerization inhibitors. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal development.
2019-06-20 | GSE132967 | GEO
Project description:The goal of this study was to compare the genomic occupancy of MAX, MNT, MGA and RNA pol II Ser5 in MAX restored versus MAX null SCLC (mRPMaxKO)
2020-06-06 | GSE146388 | GEO
Project description:Conventional crosslinked ChIP was performed on sgCtrl (control guide RNA) and sgMax (guide RNA against Max) transduced preSCs (early stage SCLC line). We find that loss of MAX leads to decreased MAX, MYC and MNT occupancy.
2020-06-06 | GSE146385 | GEO
Project description:The MYC transcription factor requires MAX for DNA binding and widespread activation of gene expression in both normal and neoplastic cells. Surprisingly, inactivating mutations in MAX are associated with a subset of neuroendocrine cancers including pheochromocytoma, pituitary adenoma and small cell lung cancer. Neither the extent nor the mechanisms of MAX tumor suppression are well understood. Deleting Max across multiple mouse neuroendocrine tissues, we find Max inactivation alone produces pituitary adenomas while Max inactivation loss cooperates with Rb1/Trp53 loss to accelerate medullary thyroid C-cell and pituitary adenoma development. In the thyroid tumor cell lines, MAX loss triggers a striking shift in genomic occupancy by other members of the MYC network (MNT, MLX, MondoA) supporting metabolism, survival and proliferation of neoplastic neuroendocrine cells. Our work reveals MAX as a broad suppressor of neuroendocrine tumorigenesis through its ability to maintain a balance of genomic occupancies among the diverse transcription factors in the MYC network.
2025-03-15 | GSE286461 | GEO
Project description:The MYC transcription factor requires MAX for DNA binding and widespread activation of gene expression in both normal and neoplastic cells. Surprisingly, inactivating mutations in MAX are associated with a subset of neuroendocrine cancers including pheochromocytoma, pituitary adenoma and small cell lung cancer. Neither the extent nor the mechanisms of MAX tumor suppression are well understood. Deleting Max across multiple mouse neuroendocrine tissues, we find Max inactivation alone produces pituitary adenomas while Max inactivation loss cooperates with Rb1/Trp53 loss to accelerate medullary thyroid C-cell and pituitary adenoma development. In the thyroid tumor cell lines, MAX loss triggers a striking shift in genomic occupancy by other members of the MYC network (MNT, MLX, MondoA) supporting metabolism, survival and proliferation of neoplastic neuroendocrine cells. Our work reveals MAX as a broad suppressor of neuroendocrine tumorigenesis through its ability to maintain a balance of genomic occupancies among the diverse transcription factors in the MYC network.
2025-03-15 | GSE286458 | GEO
Project description:CUT&RUN comparing occupancy of MAX, MNT, MYC in MAX WT and KO B220+ cells
| PRJNA549594 | ENA
Project description:The transcription factor Max is a basic helix-loop-helix leucine zipper (bHLHLZ) protein that forms homodimers or interacts with other bHLHLZ proteins, including Myc and Mxd proteins. Among this dynamic network of interactions, the Myc/Max heterodimer has crucial roles in regulating normal cellular processes, but its transcriptional activity is deregulated in a majority of human cancers. Despite this significance, the arsenal of high-quality chemical probes to interrogate these proteins remains limited. We utilized small molecule microarrays (SMMs) to identify compounds that bind Max in a mechanistically unbiased manner. We discovered the asymmetric polycyclic lactam, KI-MS2-008, which stabilizes the Max homodimer while reducing Myc protein and Myc-regulated transcript levels. KI-MS2-008 also decreases viable cancer cell growth in a Myc-dependent manner and suppresses tumor growth in vivo. This approach demonstrates the feasibility of modulating Max with small molecules and supports altering Max dimerization as an alternative approach to targeting Myc.
2019-03-14 | GSE125863 | GEO
Project description:The Myc proteins (N-, L- and c-Myc) are transcription factors involved in many biological functions such as regulation of cell proliferation, differentiation, metabolism and apoptosis. A large number of human cancers show enhanced expression of myc family proto-oncogenes as one of their hallmarks. These proteins contain a basic region/helix-loop-helix/leucine zipper (bHLHZip) domain that mediates DNA binding and heterodimerization with its partner Max (Myc/Max heterodimer). Among Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. Some reports have implied that c-Myc can perform some functions without Max in different cell contexts. However, the functional interplay in vivo between c-Myc and Max during B lymphocyte differentiation is not well-known. Here we show that c-Myc requires Max. However, key biological processes such as cell differentiation and DNA replication can initially progress without c-Myc/Max heterodimer in primary B lymphocytes. We found that B lymphocytes lacking Myc, Max or both showed upregulation of signalling pathways associated with the B cell receptor. Our data suggest that c-Myc/Max heterodimers are not essential for the initiation of certain biological processes in B lymphocytes. Rather, c-Myc/Max are necessary for fine-tuning the initial response in these cells after activation.
2018-08-20 | GSE115915 | GEO
Project description:The multi-step process of epithelial to mesenchymal transition (EMT), whereby static epithelial cells become migratory mesenchymal cells, is heavily involved in development, wound healing, and disease states. Despite the major involvement of basic helix-loop-helix (bHLH) transcription factors (TFs) in cell-fate determination, few have examined them for their involvement in fundamental processes that require EMT. Here, we have identified Max network transcription repressor (MNT) as a potent EMT promoting TF in mammary epithelium. We show that depletion of MNT blocked TGF?-induced phenotypic changes, and transcriptomic analysis revealed that MNT is a transcription repressor of epithelial identity. We show that MNT mediates repression of epithelial identity via direct interaction with HDAC1. Lastly, we show that MNT and its target genes are heavily expressed in EMT-High breast cancer, with MNT required for breast cancer cell migration. Taken together, these findings establish MNT as a critical regulator of cell-fate determination and the EMT transcriptome.
2021-09-29 | GSE158546 | GEO
Project description:Transcription factor (TF) MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs that bind to MYC increase MYC’s chromatin occupancy, which helps with MYC-mediated regulation of gene expression. Mechanistically, two highly conserved sequences, amino acids 355-357 and 364-367, in the basic region of MYC are essential for RNA binding. Notably, alanine substitution of Lys355, Arg356, and Arg357 of MYC abolishes its RNA binding function but does not influence its complex formation ability, and E-box binding capacity of MYC:MAX dimer in vitro. However, loss of RNA binding function alone decreases MYC recruitment at gene regulatory elements in vivo, followed by a decreased MYC:MAX chromatin binding at these regions. This process further attenuates MYC-mediated gene expression. Therefore, RNA-binding-deficient MYC is compromised in promoting cancer cell proliferation. By demonstrating the mechanism of MYC-RNA interaction and the fundamental role of RNA binding activity in MYC-centric functions, our study reveals a new paradigm to MYC function and highlights an essential and probably general role of RNA binding capacity of TFs for their gene regulatory function.
2025-05-08 | GSE273776 | GEO