MYC-associated factor X, MAX
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA524345 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8634200_1.fastq.gz | Fastqsanger.gz | |||
| SRR8634200_2.fastq.gz | Fastqsanger.gz | |||
| SRR8634191.fastq.gz | Fastqsanger.gz | |||
| SRR8634201_1.fastq.gz | Fastqsanger.gz | |||
| SRR8634201_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Purpose: quantitavive RT-PCR and ChIP analyses suggested that the MYC-Associated factor X, MAX, and the essential circadian regulator, BMAL1, might be recruited on the same E-box containing regulatory regions within the promoters of clock target genes. To explore this possibility, we performed ChIP-seq experiments in human cancer MDA-MB-231 cells. Methods: Chromatin samples from human cancer MDA-MB-231 cells were immunoprecipitated with specific antibodies against BMAL1 and MAX proteins. Immunoprecipitated DNA was sequenced using Illumina HiSeq 2000 sequencer. Results: ChIP-seq analysis revealed a large number of genomic regions bound by MAX (around 13000 peaks), while BMAL1 binding was limited to about 800 regions. BMAl1 and MAX bound regions comprised both promoters and distal sites. Coherently with the circadian role of BMAL1 and its preference for E-box-containing sites, ontological annotation of BMAL1 bound regions showed a significant enrichment for circadian regulated genes and E-box motifs. The 85% of the BMAL bound sites overlapped with MAX bound regions. MAX enrichment was higher on the genomic regions co-bound by BMAL1 compared with MAX binding loci sites in which BMAL1 was not present, thus indicating that MAX/BMAL1 sites are bound by MAX with high affinity. Strikingly, MAX enrichment was observed on all E-box-containing promoters of the clock core genes.
2020-04-29 | GSE127192 | GEO
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 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: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. ChIP-seq of bio-Myc and Max in E14 and respective controls; Bio-Myc ChIP-seq was performed in a stable clone of E14 mouse embryonic stem cell expressing Biotin-tagged Myc; Mock, Max and IgG were performed in parental wt E14 mESC.
2014-03-05 | E-GEOD-48175 | biostudies-arrayexpress
Project description:MYC-associated Factor X, MAX, controls the clock transcriptional network [RNA-Seq]
| PRJNA524348 | ENA
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: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
Project description:Purpose: Quantitative RT-PCR and ChIP analyses identified MAX as a transcriptional repressor of circadian BMAL1 target genes. The goal of this study is to compare the transcriptional effect of a knockdown of either MAX and BMAL1 in a human cell line (MDA-MB-231) Methods: Polyadenylated mRNA profiles of human breast cancer MDA-MB-231 cells with knocked down MAX or BMAL1 were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000 sequencer. Cells transfected with a non-targeting siRNA sequence were used as a control. RNA sequencing counts were used to determine differentially expressed genes with DeSeq2 package included in the Galaxy web platform (usergalaxy.org). Differentially expressed genes (DEGs) were defined adopting an adjust P < 0.001 as a statistical cut-off value. Results: Transcript assembly and quantification of RNA-sequencing reads identified 4863 and 4247 differentially expressed genes (DEGs) upon knockdown of BMAL1 or MAX, respectively. The comparison of the two set of genes revealed that 2391 of siBMAL1 DEGs (almost 50%) were also differentially expressed in MAX-silenced cells. Heat map and clustering analysis of this sub-set of genes revealed that more than 90% (2241 out of 2391) were coherently altered in both conditions (i.e. their expression was altered in the same direction). Consistent with our quantitative RT-PCR experiments, genes belonging to the circadian rhythm signalling were altered by both MAX and BMAL1 silencing. Conclusion: This study indicate that MAX is a part of the molecular clock transcriptional network.
2020-04-29 | GSE127212 | GEO
Project description:Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered “undruggable”, and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN- dependent manner and downregulates the MYC pathway on a global level as determined by RNA-seq. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy towards a collection of patient- derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells become G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregulates MYC/MYCN, inhibits tumor growth and prolongs survival through apoptosis with little side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for treatment of MYC-driven cancer.
2023-03-08 | GSE197062 | GEO