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The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE249179 | GEO | 2024/11/24

REPOSITORIES: GEO

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The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [RNA-seq]

Project description:Despite extensive functional and structural investigation of the Mediator complex, the basis for selective functional requirements for specific Mediator subunits for the actions of specific DNA binding transcription factors remain incompletely understood. Here, we report the MED30 subunit of Mediator, one of the core subunits maintaining the complex, plays a critical role in regulating the MYC transcription program in cancer cells. This is consequent to MED30 being required for stabilizing Mediator complex and MYC binding on the genome, involving low-affinity hydrophobic interaction functions of the MYC N-terminal Intrinsic Disordered Region (IDR). A mutational screen reveals that mutations in critical residues in the MYC coiled-coil domain structurally adjacent to the IDR of MED30 strongly inhibit tumor growth, even in the presence of wild-type MED30, mimicking the effects of MED30 deletion. This study provides new insights into the principles governing the Mediator complex actions MYC-related biological processes.

2024-11-24 | GSE249178 | GEO

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [PRO-seq]

2024-11-24 | GSE249177 | GEO

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [ChIP-seq]

2024-11-24 | GSE249335 | GEO

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program

Project description:The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program

| PRJNA1047600 | ENA

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [ChIP-seq]

Project description:The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [ChIP-seq]

| PRJNA1048545 | ENA

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [PRO-seq]

Project description:The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [PRO-seq]

| PRJNA1047607 | ENA

The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [RNA-seq]

Project description:The Role of Mediator Subunit MED30 in Licensing the c-Myc Oncogenic Program [RNA-seq]

| PRJNA1047610 | ENA

Mediator Subunit 30 Directs Myc Oncogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-08 | GSE217549 | GEO

Mediator complex proximal Tail subunit MED30 is critical for Mediator core stability and cardiomyocyte transcriptional network.

Project description:Dysregulation of cardiac transcription programs has been identified in patients and families with heart failure, as well as those with morphological and functional forms of congenital heart defects. Mediator is a multi-subunit complex that plays a central role in transcription initiation by integrating regulatory signals from gene-specific transcriptional activators to RNA polymerase II (Pol II). Recently, Mediator subunit 30 (MED30), a metazoan specific Mediator subunit, has been associated with Langer-Giedion syndrome (LGS) Type II and Cornelia de Lange syndrome-4 (CDLS4), characterized by several abnormalities including congenital heart defects. A point mutation in MED30 has been identified in mouse and is associated with mitochondrial cardiomyopathy. Very recent structural analyses of Mediator revealed that MED30 localizes to the proximal Tail, anchoring Head and Tail modules, thus potentially influencing stability of the Mediator core. However, in vivo cellular and physiological roles of MED30 in maintaining Mediator core integrity remain to be tested. Here, we report that deletion of MED30 in embryonic or adult cardiomyocytes caused rapid development of cardiac defects and lethality. Importantly, cardiomyocyte specific ablation of MED30 destabilized Mediator core subunits, while the kinase module was preserved, demonstrating an essential role of MED30 in stability of the overall Mediator complex. RNAseq analyses of constitutive cardiomyocyte specific Med30 knockout (cKO) embryonic hearts and inducible cardiomyocyte specific Med30 knockout (icKO) adult cardiomyocytes further revealed critical transcription networks in cardiomyocytes controlled by Mediator. Taken together, our results demonstrated that MED30 is essential for Mediator stability and transcriptional networks in both developing and adult cardiomyocytes. Our results affirm the key role of proximal Tail modular subunits in maintaining core Mediator stability in vivo.

| S-EPMC8432849 | biostudies-literature

Telomerase subunit TERT regulates MYC stability independent of its role on telomeres

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-04-23 | GSE60224 | GEO