The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259101 | PMC |
http://dx.doi.org/10.1038/nsmb.2914 | DOI Listing |
In Vitro Model
June 2024
In Vitro Toxicology Group, Faculty of Medicine, Health and Life Sciences, Swansea University Medical School, Swansea University, Sketty, Wales SA2 8PP UK.
Unlabelled: Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings.
View Article and Find Full Text PDFFront Immunol
January 2025
Traditional Chinese Medicine Department of Orthopaedic and Traumatic, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Colorectal cancer (CRC) is one of the most prevalent malignant tumors in the world, and its occurrence and development are closely related to the complex immune regulatory mechanisms. As the first barrier of the body's defense, innate immunity plays a key role in tumor immune surveillance and anti-tumor response, in which type I/III interferon (IFN) is an important mediator with significant antiviral and anti-tumor functions. 5-methylcytosine (m5C) modification of RNA is a key epigenetic regulation that promotes the expression of CRC oncogenes and immune-related genes.
View Article and Find Full Text PDFOncol Res
January 2025
LICIFO, Department of Restorative Sciences, Faculty of Dentistry, University of Costa Rica (HNSCC), San José, 11501, Costa Rica.
The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1's transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, China.
Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth, and neurological functions, in conjunction with mediator complex subunits 12 (MED12), MED13, and cyclin C.Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth and neurological functions,in conjunction with mediator complex subunit 12 (MED12), MED13 and cyclin C. Studying the relationship between CDK8 and cervical squamous cell carcinoma (CESC) has significant clinical implications in diagnosis, treatment, and prognosis.
View Article and Find Full Text PDFBMC Psychol
January 2025
Educational Psychology Department, Faculty of Education, Zagazig University, Sharkia, Egypt.
Background: Recent years have witnessed a revolutionary transformation in information technology, characterized by the proliferation of electronic information platforms, with the Egyptian Knowledge Bank being a notable example. Understanding how to effectively navigate these complex systems requires investigation into key factors, particularly system intelligence.
Objectives: This study aimed to examine the mediating role of research motivation in the relationship between system intelligence, Academic Grit, and Academic Achievement.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!