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Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

ABSTRACT: Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

PROVIDER: PRJNA429470 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6459175.fastq.gz	Fastqsanger.gz
	SRR6459176.fastq.gz	Fastqsanger.gz
	SRR6459177.fastq.gz	Fastqsanger.gz
	SRR6459178.fastq.gz	Fastqsanger.gz

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Similar Datasets

Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Project description:Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

| PRJNA429470 | ENA

Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Project description:The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density is one defining feature of so-called super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here we purify Mediator from neural stem cells (NSCs) and identify 77 novel protein-protein interaction partners. We identified super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalise with Mediator at enhancers and super enhancers. Three transcription factor families with high affinity for Mediator dominate enhancers and super enhancers in NSCs and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator in NSCs. Tcf4 interacts with Mediator, colocalises and correlates with Mediator at super enhancers and regulates other neural transcription factors via super enhancers. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

2019-04-01 | GSE109043 | GEO

Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Project description:Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalise with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalises with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

2019-05-06 | PXD013546 | Pride

Mediator complex interaction partners organize the transcriptional network that defines neural stem cells.

Project description:The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here, we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalize with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalizes with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

| S-EPMC6573065 | biostudies-literature

The Mediator complex in the malaria parasite Plasmodium falciparum contains evolutionarily novel subunits

Project description:The eukaryote Mediator is a large and conserved multi-subunit protein complex that directly contacts RNA polymerase II and impinges on multiple aspects of gene expression. The genome of the human malaria parasite P. falciparum has been predicted to encode several Mediator subunits. We provide physical evidence for the presence of a Mediator complex in P. falciparum by using co-immunoprecipitation and mass spectrometry to identify interaction partners of the highly conserved Mediator subunit, PfMed31. We identify 11 of 14 predicted Mediator subunits as well as the products of two uncharacterized genes, PF3D7_0526800 and PF3D7_1363600, which strongly associate with PfMed31. As expected, several additional interaction partners have known roles in the transcriptional control of gene expression and mRNA processing. Intriguingly, multiple interaction partners are implicated in endoplasmic reticulum function and the ER stress (ERS) response suggesting crosstalk between the ERS response and transcriptional machineries. Our results establish for the first time the physical presence of the Mediator complex within P. falciparum, and strongly suggest that it plays both conserved and unique roles in the control of gene expression.

2022-05-10 | PXD027640 | Pride

FOXL2 interaction with different binding partners regulates the dynamics of ovarian development

Project description:FOXL2 interaction with different binding partners regulates the dynamics of ovarian development

| PRJNA992534 | ENA

The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

Project description:The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

| PRJNA675650 | ENA

The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

Project description:The Cdk8 kinase module (CKM) is a dissociable part of the coactivator complex Mediator that regulates RNA polymerase II (Pol II transcription. The CKM has negative and positive functions in gene transcription that remain poorly understood at the mechanistic level. Here, we prepare recombinant CKM from the yeast Saccharomyces cerevisiae and show that it binds core Mediator (cMed) to sterically inhibit cMed binding to the Pol II preinitiation complex (PIC) in vitro. We further show that the Cdk8 kinase activity of CKM counteracts CKM-cMed interaction,thereby releasing CKM and enabling Mediator to bind the PIC. Finally, we report that the kinase activity of Cdk8 is required for gene activation during heat shock in vivo, but not under steady state growth conditions. These results converge with previous literature on a model for CKM function. In this model, CKM negatively regulates Mediator function at upstream activating sequences by preventing Mediator binding to the PIC at the promoter. During gene activation, Cdk8 kinase activity may release Mediator and allow its binding to the PIC, thereby stimulating transcription initiation and accounting for the positive function of CKM.

2021-06-16 | GSE161140 | GEO

Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation

Project description:Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation

| PRJEB27808 | ENA

The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

Project description:We use biochemically reconstituted transcription initiation components including the Mediator core and Cdk8 kinase modules (CKM) to investigate the function of the CKM in regulating the Mediator-RNA polymerase II interaction in a highly purified system. We use cross-linking coupled to mass spectrometry to map the interaction of the CKM and core Mediator, and in vitro phosphorylation assays followed by phosphopeptide enrichment coupled to mass spectrometry to identify Cdk8 phosphorylation targets in this context and biochemically dissect their functions. Finally, we investigate the function of phosphorylation by Cdk8 on transcription in vivo. Based on that, we propose a model to integrate the phosphorylation-dependent and -independent functions of the CKM in transcription initiation.

2021-04-28 | PXD023361 | Pride

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