Article
Cell Biology
Hongyu Zhao, Mingxin Guo, Fenghui Zhang, Xueqin Shao, Guoqing Liu, Yongqiang Xing, Xiujuan Zhao, Liaofu Luo, Lu Cai
Summary: The study proposed a chemical kinetic model of nucleosome assembly and disassembly in vitro, and confirmed the model's predictions through experiments. Using the salt dialysis method, researchers found that the efficiency of nucleosome assembly is positively correlated with the total concentration of histone octamer, reaction rate constant and reaction time.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Elena Gomez-Marin, Melanija Posavec-Marjanovic, Laura Zarzuela, Laura Basurto-Cayuela, Jose A. Guerrero-Martinez, Gonzalo Arribas, Rosario Yerbes, Maria Ceballos-Chavez, Manuel Rodriguez-Paredes, Mercedes Tome, Raul Duran, Marcus Buschbeck, Jose C. Reyes
Summary: The study reveals that PHF14 and HMG20A cooperate in regulating pathways involved in epithelial-mesenchymal plasticity, impacting cell migration, invasion, and cell-cell adhesion abilities. The PHF14-HMG20A complex modulates the Hippo pathway through direct interaction with the TEAD1 transcription factor.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Min Zhou, Linchang Dai, Chengmin Li, Liuxin Shi, Yan Huang, Zhenqian Guo, Fei Wu, Ping Zhu, Zheng Zhou
Summary: The study explores the specific functions of human histone variants H2A.B and H2A.Z.2.2 in enhancing chromatin dynamics by investigating the structural rearrangements in nucleosome core particles containing these variants. The results reveal how these variants induce unstable nucleosomes and open chromatin structures, shedding light on their critical roles in various biological processes.
Article
Biochemistry & Molecular Biology
Hongyu Zhao, Xueqin Shao, Mingxin Guo, Yongqiang Xing, Jingyan Wang, Liaofu Luo, Lu Cai
Summary: Nucleosomes are important for eukaryotic chromatin structure and regulate various biological processes. The histone variant H2A.Z can be dynamically incorporated into nucleosomes to modulate gene expression. Researchers have extended a chemical kinetic model to study the assembly dynamics of H2A.Z-containing nucleosomes. They found that the assembly efficiency of H2A.Z-containing nucleosomes is positively correlated with histone octamer concentration, reaction rate constant, and reaction time. Furthermore, they developed a competitive kinetic model to assess the competitive ability of histones in nucleosome assembly and confirmed that H2A has a higher competitive ability than H2A.Z in vitro. This study demonstrates that the assembly of H2A.Z-containing nucleosomes follows chemical kinetic principles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simon Obermeyer, Richard Stoeckl, Tobias Schnekenburger, Henna Kapoor, Thomas Stempfl, Uwe Schwartz, Klaus D. Grasser
Summary: In addition to transcriptional initiation, mRNA production is regulated during elongation, and various transcript elongation factors modulate the synthesis of mRNAs by RNA polymerase II (RNAPII) in the chromatin context. TFIIS is an elongation factor that stimulates the transcript cleavage activity of RNAPII, and its deficiency in Arabidopsis plants leads to increased sensitivity to heat stress and decreased expression of heat-induced genes. Further analysis reveals that TFIIS is required for proper RNAPII accumulation at specific nucleosomes and plays a role in reprogramming gene expression for establishing plant thermotolerance.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ashish Kumar Singh, Felix Mueller-Planitz
Summary: Eukaryotes form nucleosome particles by associating their genomes with histone proteins, which regulate and protect genetic information. These nucleosomes often assemble into evenly spaced arrays, covering significant portions of the genome, with a high degree of conservation throughout the eukaryotic domain. Various factors like transcription, nucleosome remodelers, DNA sequence, and histone density play roles in the formation of these arrays, with unanswered questions remaining about their biogenesis and cellular functions.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ravina Moirangthem, Manusha N. Gamage, Steven E. Rokita
Summary: Photochemical dimerization of adjacent pyrimidines is crucial for the creation of mutagenic hotspots, and the distribution of resulting lesions (CPDs) is highly variable in cells due to DNA conformation. Previous studies have mainly focused on mechanisms influencing CPD formation without considering CPD reversion. However, this report demonstrates that reversion is competitive under standard irradiation conditions and suggests that both CPD formation and reversion control CPD populations before reaching photo-steady-state conditions.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Pablo R. Arantes, Amun C. Patel, Giulia Palermo
Summary: In this review, established and innovative approaches used to elucidate allosteric mechanisms in protein-nucleic acid complexes are discussed. These methods, including network models derived from graph theory, molecular dynamics simulations, and ab-initio MD, offer innovative protocols to determine allosteric regulation and show promising applications in medicine and bioengineering.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Silvia Colucci, Sandro Altamura, Oriana Marques, Anne Dropmann, Natalie K. Horvat, Katja Mudder, Seddik Hammad, Steven Dooley, Martina U. Muckenthaler
Summary: The study reveals a functional link between TGF beta 1 and BMP signaling in liver sinusoidal endothelial cells (LSECs), suggesting druggable targets for iron overload diseases associated with deficiency of the BMP2-regulated hormone hepcidin, such as hereditary hemochromatosis, beta-thalassemia, and chronic liver diseases.
Review
Polymer Science
Danfeng Shi, Yuxin Huang, Chen Bai
Summary: This study summarizes the regulatory factors of the nucleosome's dynamic features from the perspective of histone modification, DNA methylation, and the nucleosome-interacting factors, and focuses on the research exploring the molecular mechanism through both computational and experimental approaches. The regulatory factors that affect the dynamic features of nucleosomes are also discussed in detail, such as unwrapping, wrapping, sliding, and stacking. The research on the functional modulation mechanism of nucleosomes faces great challenges due to the complexity of their high-order topological structures and the comprehensive effects of regulatory factors. The integration of computational and experimental approaches, the construction of physical models for nucleosomes, and the application of deep learning techniques will provide promising opportunities for further exploration.
Article
Multidisciplinary Sciences
Abrar Aljahani, Peng Hua, Magdalena A. Karpinska, Kimberly Quililan, James O. J. Davies, A. Marieke Oudelaar
Summary: Chromosome conformation capture techniques have provided insights into the 3D architecture of the genome. In this study, the authors present a high-resolution approach for generating 3C data and investigate the role of cohesin and CTCF in chromatin structure. They find that enhancers and promoters interact within large-scale topologically associating domains mediated by cohesin and CTCF. Additionally, they show that cis-regulatory elements have distinct nano-scale structures that depend on CTCF, while depletion of cohesin affects longer-range enhancer-promoter interactions.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hiroo Kenzaki, Shoji Takada
Summary: This study investigates how the folding of a nucleosome array depends on the length of linker DNA, and classifies the structure ensemble into five classes. It is found that the trinucleosome folding strongly depends on the length of linker DNA, with distinct differences in inter-nucleosome interactions observed with different linker lengths.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Bryce E. Ackermann, Galia T. Debelouchina
Summary: The eukaryotic genome is packaged into chromatin, which regulates gene expression and nuclear organization. Subtle molecular changes in chromatin can lead to global rearrangements influencing gene programs, development, and disease. MAS NMR, a relatively new technique, provides atomic level information on the complex and dynamic components of chromatin.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Fabrizio Cleri, Stefano Giordano, Ralf Blossey
Summary: This study investigates the mechanical response of chromatin to applied stress at the molecular level using a trinucleosome array as a model. The results show that DNA linkers between nucleosome pairs play a major role in accommodating compressive stress and storing elastic energy. Different mechanical instabilities can cause deformation of the DNA structure, and the histone tails assist in this deformation. Compressive stress leads to plastic deformation and localized defects in the nucleosome assembly, potentially impacting DNA transcription, signaling pathways, gene expression regulation, and DNA repair.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Deniz Dogan, Merve Arslan, Tugce Ulucay, Sibel Kalyoncu, Stefan Dimitrov, Seyit Kale
Summary: The study investigates the structural rearrangements of CENP-A nucleosomes resulting from antibody binding, showing that the antibodies can alter the dynamics of the nucleosomal core and indirectly affect the surrounding DNA. The binding of antibodies to the histone octamer surface is associated with conformational changes in CENP-A nucleosomes, indicating a more drastic impact compared to canonical nucleosomes. In addition, evidence suggests that the antibodies bind different octamer facades at varying affinities, revealing another level of complexity in DNA sequence regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stylianos Bakoulis, Robert Krautz, Nicolas Alcaraz, Marco Salvatore, Robin Andersson
Summary: Transposable elements are an abundant source of transcription factor binding sites, and they regulate gene expression in specific cell types through their association with open chromatin regions. Different subfamilies of transposable elements contribute differently to pluripotency regulatory programs through their repertoires of transcription factor binding site sequences.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Mateusz Garbulowski, Karolina Smolinska, Ugur Cabuk, Sara A. Yones, Ludovica Celli, Esma Nur Yaz, Fredrik Barrenas, Klev Diamanti, Claes Wadelius, Jan Komorowski
Summary: This study developed a methodology that corrected batch effects in glioma data and identified co-enrichment mechanisms for glioma grading using machine learning. The findings suggest potential therapeutic targets and validate the usefulness of the approach for future studies.
Article
Hematology
Svea Stratmann, Sara A. Yones, Mateusz Garbulowski, Jitong Sun, Aron Skaftason, Markus Mayrhofer, Nina Norgren, Morten Krogh Herlin, Christer Sundstrom, Anna Eriksson, Martin Hoglund, Josefine Palle, Jonas Abrahamsson, Kirsi Jahnukainen, Monica Cheng Munthe-Kaas, Bernward Zeller, Katja Pokrovskaja Tamm, Lucia Cavelier, Jan Komorowski, Linda Holmfeldt
Summary: Numerous studies have been conducted to understand the genomic and transcriptomic lesions driving acute myeloid leukemia (AML) initiation. However, there is limited knowledge about the molecular characteristics of longitudinal AML samples and the challenges of relapse and therapy resistance. Our study identified differentially expressed genes associated with short event-free survival and AML relapse, providing insights into AML progression and potential personalized drug targets.
News Item
Biochemical Research Methods
Luiz Carlos Junior Alcantara, Lucas Amenga-Etego, Robin Andersson, Moumita Bhaumik, Young Ki Choi, Helene Decaluwe, Jemma Geoghegan, Bart L. Haagmans, Susana Lopez, Maowia M. Mukhtar, Erni Nelwan, Elias A. Rahal, Kei Sato, Ella H. Sklan, Yvonne Su Chuan Fang
Summary: The article gathers opinions from scientists around the globe regarding the necessary basic research methods, tools, and resources to combat future emerging pathogenic threats.
Article
Oncology
Ulf Gyllensten, Julia Hedlund-Lindberg, Johanna Svensson, Johanna Manninen, Torbjorn Ost, Jon Ramsell, Matilda Aslin, Emma Ivansson, Marta Lomnytska, Maria Lycke, Tomas Axelsson, Ulrika Liljedahl, Jessica Nordlund, Per-Henrik Edqvist, Tobias Sjoblom, Mathias Uhlen, Karin Stalberg, Karin Sundfeldt, Mikael Aberg, Stefan Enroth
Summary: Ovarian cancer is the eighth most common cancer in women, but its survival rate is low. Current biomarkers for early detection of cancer lack sensitivity and specificity, and new biomarkers are needed. This study measured protein biomarkers and found that combinations of 4-7 proteins can accurately detect early- and late-stage ovarian cancer.
Article
Genetics & Heredity
Zhe Wang, Andrew Emmerich, Nicolas J. Pillon, Tim Moore, Daiane Hemerich, Marilyn C. Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S. Ahluwalia, Traci M. Bartz, Amy R. Bentley, Lawrence F. Bielak, Mike Chong, Audrey Y. Chu, Diane Berry, Rajkumar Dorajoo, Nicole D. Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F. Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M. Hall, Toomas Haller, Fernando P. Hartwig, David A. Hillis, Ville Huikari, Nancy Heard-Costa, Christina Holzapfel, Anne U. Jackson, Asa Johansson, Anja Moltke Jorgensen, Marika A. Kaakinen, Robert Karlsson, Kathleen F. Kerr, Boram Kim, Chantal M. Koolhaas, Zoltan Kutalik, Vasiliki Lagou, Penelope A. Lind, Mattias Lorentzon, Leo-Pekka Lyytikainen, Massimo Mangino, Christoph Metzendorf, Kristine R. Monroe, Alexander Pacolet, Louis Perusse, Rene Pool, Rebecca C. Richmond, Natalia Rivera, Sebastien Robiou-Du-Pont, Katharina E. Schraut, Christina-Alexandra Schulz, Heather M. Stringham, Toshiko Tanaka, Alexander Teumer, Constance Turman, Peter J. Van der Most, Mathias Vanmunster, Frank J. A. Van Rooij, Jana V. Van Vliet-Ostaptchouk, Xiaoshuai Zhang, Jing-Hua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie N. Balslev-Harder, Sebastian E. Baumeister, John Beilby, John Blangero, Dorret Boomsma, Soren Brage, Peter S. Braund, Jennifer A. Brody, Marcel Bruinenberg, Ulf Ekelund, Ching-Ti Liu, John W. Cole, Francis S. Collins, L. Adrienne Cupples, Tonu Esko, Stefan Enroth, Jessica D. Faul, Lindsay Fernandez-Rhodes, Alison E. Fohner, Oscar H. Franco, Tessel E. Galesloot, Scott D. Gordon, Niels Grarup, Catharina A. Hartman, Gerardo Heiss, Jennie Hui, Thomas Illig, Russell Jago, Alan James, Peter K. Joshi, Taeyeong Jung, Mika Kahonen, Tuomas O. Kilpelainen, Woon-Puay Koh, Ivana Kolcic, Peter P. Kraft, Johanna Kuusisto, Lenore J. Launer, Aihua Li, Allan Linneberg, Jian'An Luan, Pedro Marques Vidal, Sarah E. Medland, Yuri Milaneschi, Arden Moscati, Bill Musk, Christopher P. Nelson, Ilja M. Nolte, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Christine Power, Olli T. Raitakari, Magi Reedik, Alex P. Reiner, Paul M. Ridker, Igor Rudan, Kathy Ryan, Mark A. Sarzynski, Laura J. Scott, Robert A. Scott, Stephen Sidney, Kristin Siggeirsdottir, Albert Smith, Jennifer A. Smith, Emily Sonestedt, Marin Strom, E. Shyong Tai, Koon K. Teo, Barbara Thorand, Anke Toenjes, Angelo Tremblay, Andre G. Uitterlinden, Jagadish Vangipurapu, Natasja Van Schoor, Uwe Volker, Gonneke Willemsen, Kayleen Williams, Quenna Wong, Huichun Xu, Kristin L. Young, Jian Min Yuan, M. Carola Zillikens, Alan B. Zonderman, Adam Ameur, Stefania Bandinelli, Joshua C. Bis, Michael Boehnke, Claude Bouchard, Daniel Chasman, George Davey Smith, Eco J. C. De Geus, Louise Deldicque, Marcus Dorr, Michele K. Evans, Luigi Ferrucci, Myriam Fornage, Caroline Fox, Theodore Garland, Vilmundur Gudnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo L. Horta, Elina Hypponen, Marjo-Riitta Jarvelin, W. Craig Johnson, Sharon L. R. Kardia, Lambertus A. Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimaki, Loic Le Marchand, Patrik K. E. Magnusson, Nicholas G. Martin, Mads Melbye, Andres Metspalu, David Meyre, Kari E. North, Claes Ohlsson, Albertine J. Oldehinkel, Marju Orho-Melander, Guillaume Pare, Taesung Park, Oluf Pedersen, Brenda W. J. H. Penninx, Tune H. Pers, Ozren Polasek, Inga Prokopenko, Charles N. Rotimi, Nilesh J. Samani, Xueling Sim, Harold Snieder, Thorkild I. A. Sorensen, Tim D. Spector, Nicholas J. Timpson, Rob M. Van Dam, Nathalie Van der Velde, Cornelia M. Van Duijn, Peter Vollenweider, Henry Volzke, Trudy Voortman, Gerard Waeber, Nicholas J. Wareham, David R. Weir, Heinz-Erich Wichmann, James F. Wilson, Andrea L. Hevener, Anna Krook, Juleen R. Zierath, Martine A. Thomis, Ruth J. F. Loos, Marcel Den Hoed
Summary: Physical activity and sedentary behavior have genetic components, and this study identified 99 genetic loci associated with self-reported physical activity, leisure screen time, and sedentary behavior. Some genetic variants were found to affect muscle function and possibly protect against exercise-induced muscle damage. Mendelian randomization analyses also revealed that the beneficial effects of reducing sedentary behavior and increasing physical activity on health outcomes may be mediated or confounded by body mass index.
Review
Biochemistry & Molecular Biology
Judith Barbara Zaugg, Pelin Sahlen, Robin Andersson, Meritxell Alberich-Jorda, Wouter de Laat, Bart Deplancke, Jorge Ferrer, Susanne Mandrup, Gioacchino Natoli, Dariusz Plewczynski, Alvaro Rada-Iglesias, Salvatore Spicuglia
Summary: Enhancers are crucial for the spatiotemporal control of gene expression and are cell-type-specific. They are suggested to contribute to phenotypic variation, evolution, and disease. Dysfunction of enhancers, caused by genetic, structural, or epigenetic mechanisms, has been linked to a broad range of human diseases, known as enhanceropathies. Understanding how enhancer dysfunction affects gene expression remains a challenge.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biology
Hjoerleifur Einarsson, Marco Salvatore, Christian Vaagenso, Nicolas Alcaraz, Jette Bornholdt, Sarah Rennie, Eduardo Eyras, Robin Andersson
Summary: This study investigates the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. The results show that expression variability can be largely explained by a promoter's DNA sequence and its binding sites for specific transcription factors. Additionally, the study reveals a trade-off between stability and plasticity for different types of genes.
Article
Biochemistry & Molecular Biology
Lucas van Duin, Robert Krautz, Sarah Rennie, Robin Andersson
Summary: This study investigates the regulatory determinants of gene co-activity in genomic domains using individual variation in gene expression. The researchers identify co-regulatory processes underlying co-activity and quantify their effect sizes. They find that transcription factor expression levels are the main determinant of gene co-activity, with distal trans effects contributing more than local genetic variation.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Chemistry, Analytical
Salvador Daniel Rivas-Carrillo, Evgeny E. E. Akkuratov, Hector Valdez Ruvalcaba, Angel Vargas-Sanchez, Jan Komorowski, Daniel San-Juan, Manfred G. G. Grabherr
Summary: Electroencephalogram (EEG) interpretation is crucial in assessing neurological conditions, especially epilepsy. Manual analysis of EEG recordings is time-consuming and expensive. Automatic detection, like MindReader, offers the potential to shorten diagnosis time and optimize resource allocation. MindReader utilizes an autoencoder network, hidden Markov model (HMM), and generative component to generate labels for pathological and non-pathological phases, reducing the search space for trained personnel. Evaluation on 686 recordings showed MindReader's high sensitivity in detecting epileptic events (99.45%).
Article
Geriatrics & Gerontology
Taoyu Mei, Yuan Li, Anna Orduna Dolado, Zhiquan Li, Robin Andersson, Laura Berliocchi, Lene Juel Rasmussen
Summary: The growing prevalence of Alzheimer's disease (AD) is a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have been suggested as etiological factors in AD. This study integrated transcriptomic data from AD and healthy patients to identify mitophagy-related genes and validate their expression changes in AD-relevant human in vitro models.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Marco Salvatore, Marc Horlacher, Annalisa Marsico, Ole Winther, Robin Andersson
Summary: Dysfunction of regulatory elements through genetic variants is a central mechanism in disease pathogenesis. Deep learning methods have shown promise in modeling biomolecular data from DNA sequence but require large input data for training. ChromTransfer, a transfer learning method, utilizes a pre-trained model of open chromatin regions to fine-tune on regulatory sequences and demonstrates superior performance in learning cell-type specific chromatin accessibility. It is able to fine-tune on small input data with minimal decrease in accuracy and utilizes sequence features matching binding site sequences of key transcription factors for prediction, making it a promising tool for learning the regulatory code.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Article
Cell Biology
Klev Diamanti, Marco Cavalli, Maria J. Pereira, Gang Pan, Casimiro Castillejo-Lopez, Chanchal Kumar, Filip Mundt, Jan Komorowski, Atul S. Deshmukh, Matthias Mann, Olle Korsgren, Jan W. Eriksson, Claes Wadelius
Summary: Environmental and genetic factors contribute to defects in pancreatic islets and insulin resistance in type 2 diabetes (T2D). Through proteomic analysis of multiple metabolic tissues, we identified tissue-specific metabolic dysregulations in T2D, including inflammatory, immune, and vascular alterations.
CELL REPORTS MEDICINE
(2022)
Article
Medicine, Research & Experimental
Stefan Enroth, Emma Ivansson, Julia Hedlund Lindberg, Maria Lycke, Jessica Bergman, Anna Reneland, Karin Stalberg, Karin Sundfeldt, Ulf Gyllensten
Summary: This study developed a risk score based on an 11-protein plasma assay to distinguish between benign and malignant ovarian tumors. The assay showed robust performance in diagnostic work-up and predicting clinical course.
COMMUNICATIONS MEDICINE
(2022)
Meeting Abstract
Veterinary Sciences
Fredrik Barrenas, Scott Hansen, Lynn Law, Connor Driscoll, Richard Green, Elise Smith, Jean Chang, Inah Golez, Taryn Urion, Xinxia Peng, Leanne Whitmore, Daniel Newhouse, Colette Hughes, David Morrow, Kurt Randall, Andrea Selseth, Julia Ford, Roxanne Gilbride, Bryan Randall, Emily Ainslie, Kelli Oswald, Rebecca Shoemaker, Randy Fast, William Bosche, Michael Axthelm, Yoshinori Fukazawa, George Pavlakis, Barbara Felber, Slim Fourati, Sekaly Rafick-Pierre, Jeffrey Lifson, Jan Komorowski, Ewelina Kosmider, Danica Shao, Wenjun Song, Paul Edlefsen, Louis Picker, Michael Gale
JOURNAL OF MEDICAL PRIMATOLOGY
(2022)