Mechanisms of activation of interferon regulator factor 3: the role of C-terminal domain phosphorylation in IRF-3 dimerization and DNA binding

The interferon regulatory transcription factor (IRF-3) is activated by phosphorylation of Ser/Thr residues clustered in its C-terminal domain. Phosphorylation of these residues, which increases the negative charge of IRF-3, results in its dimerization and association with DNA, despite the increase in repulsive electrostatic interactions. To investigate this surprising effect, the dimerization of IRF-3 and two phosphomimetic mutants, 2D (S396D, S398D) and 5D (S396D, S398D, S402D, T404D and S405D), and their binding to single-site PRDI and double-site PRDIII–PRDI DNA sequences from the IFN-β enhancer have been studied. It was found that: (a) the mutations in the C-terminal domain do not affect the state of the DNA-binding N-terminal domain or its ability to bind target DNA; (b) in the 5D-mutant, the local increase of negative charge in the C-terminal domain induces restructuring, resulting in the formation of a stable dimer; (c) dimerization of IRF-3 is the basis of its strong binding to PRDIII–PRDI sites since binding of 5D to the single PRDI site is similar to that of inactivated IRF-3. Analysis of the binding characteristics leads to the conclusion that binding of dimeric IRF-3 to the DNA with two tandem-binding sites, which are twisted by ∼100° relative to each other, requires considerable work to untwist and/or bend the DNA

BioDATA - Biodiversity Data for Internationalisation in Higher Education

BioDATA is an international project on developing skills in biodiversity data management and data publishing. Between 2018 and 2021, undergraduate and postgraduate students from Armenia, Belarus, Tajikistan, and Ukraine, have an opportunity to take part in the intensive courses to become certified professionals in biodiversity data management. They will gain practical skills and obtain appropriate knowledge on: international data standards (Darwin Core); data cleaning software, data publishing software such as the Integrated Publishing Toolkit (IPT), and preparation of data papers. Working with databases, creating datasets, managing data for statistical analyses and publishing research papers are essential for the everyday tasks of a modern biologist. At the same time, these skills are rarely taught in higher education. Most of the contemporary professionals in biodiversity have to gain these skills independently, through colleagues, or through supervision. In addition, all the participants familiarize themselves with one of the important international research data infrastructures such as the Global Biodiversity Information Facility (GBIF). The project is coordinated by the University of Oslo (Norway) and supported by the Global Biodiversity Information Facility (GBIF). The project is funded by the Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education (DIKU)

DNA-binding domain of GCN4 induces bending of both the ATF/CREB and AP-1 binding sites of DNA

The interaction of proteins with DNA results, in some cases, in DNA bending, and this might have functional importance. However, when the protein-induced bending of DNA is small, its measurement presents a problem. It is shown that the fluorescence resonance energy transfer between fluorophores placed on the ends of the specially designed U-shaped DNA, which contains the DNA-binding sites at its central part, can be successfully used for this purpose. The lever effect of the arms of such U-shaped DNA ensures that the distance between the fluorophores is very sensitive to bending of the central part. Using this technique, it was shown that (i) the AP-1 and ATF/CREB binding sites of GCN4 transcription factor are pre-bent to the same extent (∼12° toward the major groove) and (ii) binding of the GCN4 DNA-binding domain (GCN4-bZIP) results in additional bending of both these target sites but to a greater extent at the ATF/CREB site. In total, in the complex with GCN4-bZIP, the ATF/CREB site is bent by (25 ± 2)° and the AP-1 site by (20 ± 2)° toward the minor groove

BioDATA: Biodiversity data mobilisation and data publication training in Eurasia

BioDATA (Biodiversity Data for Internationalisation in Higher Education) is an international project to develop and deliver biodiversity data training for undergraduate and postgraduate students from Armenia, Belarus, Tajikistan, and Ukraine. By training early career (student) biodiversity scholars, we aim at turning the current academic and education biodiversity landscape into a more open-data-friendly one. Professional practitioners (researchers, museum curators, and collection managers involved in data publishing) from each country were also invited to join the project as assistant teachers (mentors). The project is developed by the Research School in Biosystematics - ForBio and the Norwegian GBIF-node, both at the Natural History Museum of the University of Oslo in collaboration with the Secretariat of the Global Biodiversity Information Facility (GBIF) and partners from each of the target countries. The teaching material is based on the GBIF curriculum for data mobilization and all students will have the opportunity to gain the respective GBIF certification. All materials are made freely available for reuse and even in this very early phase of the project, we have already seen the first successful reuse of teaching materials among the project partners. The first BioDATA training event was organized in Minsk (Belarus) in February 2019 with the objective to train a minimum of four mentors from each target country. The mentor-trainees from this event will help us to teach the course to students in their home country together with teachers from the project team. BioDATA mentors will have the opportunity to gain GBIF certification as expert mentors which will open opportunities to contribute to future training events in the larger GBIF network. The BioDATA training events for the students will take place in Dushanbe (Tajikistan) in June 2019, in Minsk (Belarus) in November 2019, in Yerevan (Armenia) in April 2020, and in Kiev (Ukraine) in October 2020. Students from each country are invited to express their interest to participate by contacting their national project partner. We will close the project with a final symposium at the University of Oslo in March 2021. The project is funded by the Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education (DIKU)