Eukaryotic gene expression requires the coordination of multiple factors to overcome the repressive nature of chromatin. However, the mechanistic details of this coordination are not well understood. The SAGA family of transcriptional coactivators interacts with DNA-binding activators to establish regions of hyperacetylation. We have previously shown that, contrary to the prevailing model in which activator protein increases SAGA affinity for nucleosome substrate, the Gal4-VP16 activator model system augments the rate of acetylation turnover for the SAGA complex from budding yeast. To better understand how this stimulation occurs, we have identified necessary components using both kinetics assays and binding interactions studies. We find that Gal4-VP16-mediated stimulation requires activator binding to DNA flanking the nucleosome, as it cannot be reproduced by activator protein alone or by exogenous DNA containing the activator binding site in combination with the activator protein. Further, activator-mediated stimulation requires subunits outside of the histone acetylation (HAT) module, with the Tra1 subunit being responsible for the majority of the stimulation. Interestingly, for the HAT module alone, nucleosome acetylation is inhibited by activator proteins due to non-specific binding of the activator to the nucleosomes. This inhibition is not observed for the yeast ADA complex, a small complex comprised mostly of the HAT module, suggesting that subunits outside of the HAT module in both it and SAGA can overcome non-specific activator binding to nucleosomes. However, this activity appears distinct from activator-mediated stimulation, as ADA complex acetylation is not stimulated by Gal4-VP16.
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http://dx.doi.org/10.1016/j.bbrep.2020.100884 | DOI Listing |
HNO
January 2025
Universitätsklinik für Hals‑, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie Innsbruck, Medizinische Universität Innsbruck, Anichstr. 35, 6020, Innsbruck, Österreich.
Background: Electronically captured patient reports (electronic patient-reported outcomes, ePROs) are digital questionnaires filled out by cancer patients. Despite indications of improved clinical care, the integration of ePROs into clinical head and neck oncology is uncharted territory.
Objective: This work outlines the implementation process for ePROs at the University Hospital for Otorhinolaryngology at the Medical University of Innsbruck (ENT Innsbruck).
Nucleic Acids Res
January 2025
Ohio State Biochemistry Program, Ohio State University, 191 W. Woodruff Ave. Columbus, OH, 43210, USA.
Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruit transcription coactivators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5 acetyltransferase), containing histone acetyltransferase (HAT) activity, target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA HAT complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions.
View Article and Find Full Text PDFMaterials (Basel)
November 2024
Flexible Manufacturing R&D Department, Korea Institute of Industrial Technology, Incheon 21999, Republic of Korea.
This study investigates the effects of hot stamping on boron steel surface properties, comparing uncoated steel to Al-Si-coated steel, with a focus on developing atmosphere-controlled hot stamping technology. Experiments using a hat-shaped specimen revealed that uncoated steel formed a thick oxide layer due to exposure to atmospheric oxygen at high temperatures, negatively impacting surface quality and weldability. In contrast, the Al-Si-coated steel showed no oxide formation.
View Article and Find Full Text PDFLight Sci Appl
June 2024
European Molecular Biology Laboratory, Cell Biology and Biophysics, Heidelberg, Germany.
MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore tracking. It is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity minimum. Current implementations, however, are complex and expensive and are limited in speed and robustness.
View Article and Find Full Text PDFAnal Chem
May 2024
SCIEX, 71 Four Valley Drive, Concord, Ontario L4K 4V8, Canada.
Pharmacological screening heavily relies on the reliability of compound libraries. To ensure the accuracy of screening results, fast and reliable quality control (QC) of these libraries is essential. While liquid chromatography (LC) with ultraviolet (UV) or mass spectrometry (MS) detection has been employed for molecule QC on small sample sets, the analytical throughput becomes a bottleneck when dealing with large libraries.
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