An evolutionarily conserved complex, the Mediator, is a key partner of most transcriptional activators in eukaryotes [1]. Gal11 and ARC105 are Mediator subunits linking specific transcriptional activators to the basal transcription apparatus [2,3]. Gal11 is part of the proposed " Gal11 module " , in which it has been suggested to be a direct target of several activators [4]. However, the existe...

Abstract The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in repression and through binding to Gal80 repressor Mediator subunit Med15. function arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds Med15 using “fuzzy” protein interface. Remarkably, comparison chemical shift perturbations shows Gcn4, intrinsic...

The X-ray crystal structure of the Head module, one-third of the Mediator of transcriptional regulation, has been determined as a complex with the C-terminal domain (CTD) of RNA polymerase II. The structure reveals multiple points of interaction with an extended conformation of the CTD; it suggests a basis for regulation by phosphorylation of the CTD. Biochemical studies show a requirement for ...

A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interact...

The clinical domain of cognitive diseases and dementia is recognized by its highly complex knowledge domain, requiring expertise and experience in handling situations with a variety of symptoms and diseases, distributed over different levels in organizations and different professions. In this paper a pilot study is presented where eight experienced physicians in Sweden and Japan used an early p...

Mutations in three subunits of the SWI/SNF complex and in the Med2p subunit of the SRB/mediator of pol II holoenzyme impaired Gcn4p-activated transcription of HIS3 without reducing Gcn4p-independent transcription of this gene. Recombinant Gcn4p interacted with SWI/SNF and SRB/mediator subunits in cell extracts in a manner dependent on the same hydrophobic clusters in the Gcn4p activation domain...

The interaction of activators with mediator has been proposed to stimulate the assembly of RNA polymerase II (Pol II) preinitiation complexes, but there have been few tests of this model. The finding that the major adenovirus E1A and mitogen-activated protein kinase-phosphorylated Elk1 activation domains bind to Sur2 uniquely among the metazoan mediator subunits and the development of transcrip...

The N-terminal acidic transactivation domain (TAD) of ERM/ETV5 (ERM38-68), a PEA3 group member of Ets-related transcription factors, directly interacts with the ACID/PTOV domain of the Mediator complex subunit MED25. Molecular details of this interaction were investigated using nuclear magnetic resonance (NMR) spectroscopy. The TAD is disordered in solution but has a propensity to adopt local t...

Mutations in NLRP7 (NOD-like-receptor family, pyrin domain containing 7) are responsible for a type of recurrent pregnancy loss known as recurrent hydatidiform mole (HYDM1). This condition is characterized by abnormal growth of the placenta, a lack of proper embryonic development and abnormal methylation patterns at multiple imprinted loci in diploid biparental molar tissues. The role of NLRP7 ...