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Mature chromatin packing domains persist after RAD21 depletion in 3D.
Sci Adv
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.
View Article and Find Full Text PDFElucidating assembly and function of VirB8 cell wall subunits refines the DNA translocation model in Gram-positive T4SSs.
Sci Adv
January 2025
Université de Lorraine, INRAE, DynAMic, F-54000 Nancy, France.
Bacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria.
View Article and Find Full Text PDFSequence-Defined DNA Polymers: New Tools for DNA Nanotechnology and Nucleic Acid Therapy.
Acc Chem Res
January 2025
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
ConspectusStructural DNA nanotechnology offers a unique self-assembly toolbox to construct soft materials of arbitrary complexity, through bottom-up approaches including DNA origami, brick, wireframe, and tile-based assemblies. This toolbox can be expanded by incorporating interactions orthogonal to DNA base-pairing such as metal coordination, small molecule hydrogen bonding, π-stacking, fluorophilic interactions, or the hydrophobic effect. These interactions allow for hierarchical and long-range organization in DNA supramolecular assemblies through a DNA-minimal approach: the use of fewer unique DNA sequences to make complex structures.
View Article and Find Full Text PDFProbing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.
bioRxiv
December 2024
Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence.
View Article and Find Full Text PDFH3K56 acetylation regulates chromatin maturation following DNA replication.
Nat Commun
January 2025
Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Following DNA replication, the newly reassembled chromatin is disorganized and must mature to its steady state to maintain both genome and epigenome integrity. However, the regulatory mechanisms governing this critical process remain poorly understood. Here, we show that histone H3K56 acetylation (H3K56ac), a mark on newly-synthesized H3, facilitates the remodeling of disorganized nucleosomes in nascent chromatin, and its removal at the subsequent G2/M phase of the cell cycle marks the completion of chromatin maturation.
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