Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.
Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation
Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein
The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids.
Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation
The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain.
Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription
p300 interacts with the N- and C-terminal part of PPARgamma2 in a ligand-independent and -dependent manner, respectively.
The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response
Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo
Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains
The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex
Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming
Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains
KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks
What is the switch for coupling transcription and splicing? RNA Polymerase II C-terminal domain phosphorylation, phase separation and beyond
IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions-Insights from transcription factors
Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling
rDNA Clusters Make Contact with Genes that Are Involved in Differentiation and Cancer and Change Contacts after Heat Shock Treatment
Multifaceted function of YAP/TEAD on chromatin:prospects of 'A non-canonical role of YAP/TEAD is required for activation of estrogen-regulated enhancers in breast cancer'
Kethoxal-assisted single-stranded DNA sequencing captures global transcription dynamics and enhancer activity in situ.
The regulatory landscape of the Dlx gene system in branchial arches: shared characteristics among Dlx bigene clusters and evolution
Dissecting the transactivation domain (tAD) of the transcription factor c-Myb to assess recent models of tAD function.
Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors
Mediator complex subunit Med19 binds directly GATA transcription factors and is required with Med1 for GATA-driven gene regulation in vivo.
Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions
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