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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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: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:The MYC-axis is disrupted in cancer, mostly by activation of the MYC-oncogenes but also through inactivation of the MYC-partner, MAX, or of the MAX-partner, MGA, both also members of the polycomb repressive complex, ncPRC1.6. Here, we use genetically modified MAX-deficient small cell lung cancer (SCLC) cells and apply genome wide and proteomics analysis to study the tumor suppressor function of MAX. We find that MAX-mutant SCLCs classify as ASCL1-type and lack MYC-transcriptional activities. MAX-restitution triggers pro-differentiation expression profiles that shift when MAX and oncogenic MYC (HMYC/MAX) are co-expressed. Despite the ncPRC1.6 can be formed, the lack of MAX restricts global MGA-occupancy, selectively driving its recruitment towards E2F6-motifs. Conversely, MAX-restitution enhances MGA-occupancy and global gene repression of genes involved in different functionalities, including stem-cell and DNA repair/replication. Collectively, these findings reveal that MAX-mutant SCLCs have ASCL1-characteristics, are MYC-independent and their oncogenic features include a deficient ncPRC1.6-mediated gene repression.
2021-01-18 | GSE144457 | GEO
Project description:The MYC axis is commonly disrupted in cancer, mostly by activation of the MYC family of oncogenes, but also by genetic inactivation of MAX, the obligate partner of MYC, and of the MAX partner, MGA, both of which are members of the polycomb repressive complex, ncPRC1.6. While the oncogenic properties of the MYC family have been extensively studied, the tumor suppressor functions of MAX and MGA and the role of the MYC genes in MAX-mutant cells remain unclear. To address these knowledge gaps, we used chromatin immunoprecipitation, RNA-sequencing and mass spectrometry-based proteomic analysis in MAX-restituted and MYC oncogenic-transformed cell lines derived from human small cell lung cancer (SCLC), which is a high-grade neuroendocrine type of lung cancer. We found that MAX-mutant SCLC cells express ASCL1 and ASCL1-dependent targets, implying that these cells belong to the ASCL1-dependent group of SCLCs. In the absence of MAX, even after ectopic overexpression of MYC, we found no recruitment of MYC to the DNA. Furthermore, MAX reconstitution triggered pro-differentiation expression profiles that shifted when MAX and oncogenic MYC were co-expressed. Although ncPRC1.6 could be formed, the lack of MAX restricted global MGA occupancy, selectively driving its recruitment towards E2F6 motifs. Conversely, MAX restitution enhanced MGA occupancy and global gene repression of genes involved in different functions, including stem-cell and DNA repair/replication. Our data reveal that MAX-mutant SCLCs have ASCL1 characteristics, and are MYC-independent, and that their oncogenic features include deficient ncPRC1.6-mediated gene repression.
2021-09-22 | PXD017658 | Pride
Project description:Myc is a master transcription factor that has been demonstrated to be required for embryonic stem cell (ESC) pluripotency, self-renewal, and inhibition of differentiation. Although recent works identified several Myc-targets in ESC the list of Myc binding sites is largely incomplete due to the low sensitivity and specificity of the antibodies available so far. To systematically identify Myc binding sites in mouse ESCs here we used a stringent streptavidin based genome-wide chromatin immunoprecipitation (ChIP-Seq) of a biotin-tagged Myc (Bio-Myc) as well as a ChIP-Seq of the Myc partner Max. This analysis identified 4273 Myc binding sites of which more than 85% co-occupied by Max, overlap with H3K4me3 positive promoters and active enhancers of transcriptional regulators, chromatin modifiers, and genes involved in stem cell self-renewing. The new sites identified were validated experimentally. This study provides a new Myc and Max binding reference in mouse ESCs.
2014-03-05 | GSE48175 | GEO