Review
Biophysics
T. Man, H. Witt, E. J. G. Peterman, G. J. L. Wuite
Summary: Condensation and faithful separation of the genome are essential for the cellular life cycle, and mechanical properties of mitotic chromosomes remain a topic of interest. Recent advances in genomics and microscopy techniques have improved understanding of chromosomal structure, leading to a focus on mechanical characteristics and their relationship to chromosome structure.
QUARTERLY REVIEWS OF BIOPHYSICS
(2021)
Article
Biochemical Research Methods
Yan Li, Lijun Quan, Yiting Zhou, Yelu Jiang, Kailong Li, Tingfang Wu, Qiang Lyu
Summary: This article proposes a deep learning-based multi-objective computational approach, iHMnBS, to accurately identify histone modifications in DNA sequences and their binding sites. By mining richer data information and utilizing deep neural networks, iHMnBS outperforms other methods in performance and serves as a reference for biological experiments.
Article
Multidisciplinary Sciences
Chun-Yi Cho, Patrick H. O'Farrell
Summary: Eukaryotic transcription is initiated by the recruitment of transcription factors (TFs), coactivators, and preinitiation complexes. Live imaging of endogenously tagged proteins in early Drosophila embryos reveals a cascade of events upstream of transcriptional initiation. Sequential and transient recruitment of TFs, coactivators, and RNA polymerase II (RNAPII) occurs in discrete clusters during the activation of non-histone genes. This study suggests that eukaryotic transcription involves a succession of distinct biomolecular condensates, culminating in a self-limiting burst of transcription.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Benjamin D. Sunkel, Meng Wang, Stephanie LaHaye, Benjamin J. Kelly, James R. Fitch, Frederic G. Barr, Peter White, Benjamin Z. Stanton
Summary: This study quantitatively examines the role of PFs in childhood rhabdomyosarcoma and finds that PAX3-FOXO1 has the ability to localize in inactive chromatin and nucleosome motifs.
Review
Engineering, Biomedical
Chad M. Hobson, Michael R. Falvo, Richard Superfine
Summary: The cell nucleus is not just a location for DNA, but also a complex material that resists physical deformations and dynamically responds to external mechanical cues. The molecules responsible for nuclear mechanical properties can contribute to laminopathies and potentially play a role in cellular mechanotransduction and physical processes in cancer. Studying nuclear mechanics and the downstream biochemical consequences or their modulation requires a suite of complex assays for applying, measuring, and visualizing mechanical forces across diverse length, time, and force scales.
APL BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Jan Bohning, Tanmay A. M. Bharat, Sean M. Collins
Summary: Cryoelectron tomography and subtomogram averaging enable direct visualization and study of biological macromolecules in their native cellular environment. However, limitations such as low signal-to-noise ratios, low particle abundance, and low throughput have restricted the obtainable structural information. This study demonstrates the potential of a compressed sensing approach to enhance the visualization and resolution of tomograms, addressing these limitations.
Article
Biochemistry & Molecular Biology
Matthew Herdman, Andriko von Kugelgen, Danguole Kureisaite-Ciziene, Ramona Duman, Kamel El Omari, Elspeth F. Garman, Andreas Kjaer, Dimitrios Kolokouris, Jan Lowe, Armin Wagner, Phillip J. Stansfeld, Tanmay A. M. Bharat
Summary: In this study, the role of metal ions in the formation of Caulobacter crescentus S-layer was investigated. It was found that calcium ions facilitate S-layer lattice formation and cell-surface binding, and that bound metal ions are crucial for the S-layer lattice. The positions of metal ions in the S-layer were also mapped using advanced imaging techniques. These findings contribute to the understanding of S-layer formation and have implications for synthetic biology.
Article
Multidisciplinary Sciences
Byung-Gil Lee, James Rhodes, Jan Lowe
Summary: The condensin complex is responsible for compacting DNA into chromatids during mitosis. This study provides molecular insights into the structural dynamics of the complex and reveals differences in the behavior of its subunits. The findings will contribute to our understanding of the mechanism of DNA compaction by SMC complexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mathew Van de Pette, Antonio Galvao, Steven J. Millership, Wilson To, Andrew Dimond, Chiara Prodani, Grainne McNamara, Ludovica Bruno, Alessandro Sardini, Zoe Webster, James McGinty, Paul French, Anthony G. Uren, Juan Castillo-Fernandez, Rosalind M. John, Anne C. Ferguson-Smith, Matthias Merkenschlager, Gavin Kelsey, Amanda G. Fisher, William Watkinson
Summary: This study demonstrates that a high-fat diet in pregnant mice can lead to the release of silencing of the Dlk1 gene locus in multiple generations of offspring. The authors found that this occurs through changes in microRNA expression and transcriptional changes in the developing oocytes. These findings highlight how diet can impact the fetal epigenome, affecting the properties of successive generations of offspring through intergenerational or trans-generational mechanisms.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Multidisciplinary Sciences
Jan Lowe
Summary: A microorganism, believed to be a relative of our cellular ancestors, has been successfully cultured in the laboratory, providing insights into the early evolution of eukaryotic cells.
Editorial Material
Biochemical Research Methods
Olivia E. R. Smith, Tanmay A. M. Bharat
Summary: DeepPiCt, a deep learning approach, enables segmentation and identification of macromolecules in the cellular jungle of electron cryotomography data.
Article
Genetics & Heredity
Viraat Y. Goel, Miles K. Huseyin, Anders S. Hansen
Summary: The researchers developed a method called Region Capture Micro-C (RCMC), which combines MNase-based 3C with a tiling region-capture approach to generate deep 3D genome maps. Using RCMC in mouse embryonic stem cells, they discovered previously unresolvable patterns of highly nested and focal 3D interactions, termed microcompartments, which frequently connect enhancers and promoters. Most microcompartments are largely unaffected by loss of loop extrusion and transcription inhibition, suggesting that many enhancer-promoter interactions form through a compartmentalization mechanism.
Article
Biochemistry & Molecular Biology
Dounia Djeghloul, Andrew Dimond, Sherry Cheriyamkunnel, Holger Kramer, Bhavik Patel, Karen Brown, Alex Montoya, Chad Whilding, Yi-Fang Wang, Matthias E. Futschik, Nicolas Veland, Thomas Montavon, Thomas Jenuwein, Matthias Merkenschlager, Amanda G. Fisher
Summary: Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In this study, the researchers found that enzymes that catalyze H3K9 methylation are also retained on mitotic chromosomes. Mutants lacking H3K9me3 display unusually small and compact mitotic chromosomes, but this phenotype can be rescued by providing exogenous protein lysine methyltransferase or inhibiting Ezh2 activity. These findings highlight the important role of H3K9me3 in maintaining chromosome architecture and epigenetic memory during cell division.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Microbiology
Lisa Kashammer, Fusinita van den Ent, Magnus Jeffery, Nicolas L. Jean, Victoria L. Hale, Jan Lowe
Summary: The cryogenic electron microscopy structure of the Pseudomonas aeruginosa cell division complex and antibiotic drug target, FtsWIQBL, suggests a possible activation mechanism involving a large conformational change in the periplasmic domain. Our work reveals intricate structural details and explains the consequences of previously reported mutations. The FtsWIQBL complex is central to the divisome and understanding its precise mechanism is important for the design of future experiments and development of antibiotics.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
James Mark Wagstaff, Vicente Jose Planelles-Herrero, Grigory Sharov, Aisha Alnami, Frank Kozielski, Emmanuel Derivery, Jan Lowe
Summary: Protein filaments are used to organize other molecules within cells, and some of them can generate movement by coupling nucleotide hydrolysis to their polymerization cycle. Actin and tubulin proteins are capable of forming cytomotive filaments. In this study, the polymerization cycles of actin and tubulin homologs were analyzed to understand the basis of cytomotivity. Shared subunit polymerization switches were found in cytomotive actins and tubulins, indicating conformational changes of subunits upon filament assembly. These cytomotive switches contribute to filament robustness and ensure their stability.
Article
Multidisciplinary Sciences
Fredrik Hurtig, Thomas C. Q. Burgers, Alice Cezanne, Xiuyun Jiang, Frank N. Mol, Jovan Traparic, Andre Arashiro Pulschen, Tim Nierhaus, Gabriel Tarrason-Risa, Lena Harker-Kirschneck, Jan Lowe, Andela Saric, Rifka Vlijm, Buzz Baum
Summary: ESCRT-III family proteins form composite polymers that deform and cut membrane tubes in cell biological processes. Using Sulfolobus acidocaldarius as a model, researchers demonstrated how CdvB/CdvB1/CdvB2 proteins form a patterned composite ESCRT-III division ring and undergo Vps4-dependent disassembly to cut cells. Sequential changes in the patterned composite polymer may be a general mechanism of ESCRT-III-dependent membrane remodeling.
Article
Biology
Hannah J. J. Gleneadie, Beatriz Fernandez-Ruiz, Alessandro Sardini, Mathew Van de Pette, Andrew Dimond, Rab K. K. Prinjha, James McGinty, Paul M. W. French, Hakan Bagci, Matthias Merkenschlager, Amanda G. G. Fisher
Summary: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene (Dmd), leading to progressive muscle weakening. A study using mouse models and myoblasts found that chromatin-modifying drugs can increase the expression of utrophin (Utrn), a protein that can compensate for Dmd deficiency. Inhibitors of PRC2 and ERK1/2 were identified to enhance Utrn expression, offering potential therapeutic strategies for DMD.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Tim K. Esser, Jan Bohning, Paul Fremdling, Mark T. Agasid, Adam Costin, Kyle Fort, Albert Konijnenberg, Joshua D. Gilbert, Alan Bahm, Alexander Makarov, Carol V. Robinson, Justin L. P. Benesch, Lindsay Baker, Tanmay A. M. Bharat, Joseph Gault, Stephan Rauschenbach
Summary: Despite advances in cryo-EM and SPA, sample heterogeneity remains a challenge. The study demonstrates the potential of native ES-IBD as an alternative approach for preparing high-purity samples. This method has the potential to increase the scope and throughput of cryo-EM for protein structure determination.
