Article
Multidisciplinary Sciences
Brian Chan, Michael Rubinstein
Summary: The active loop extrusion hypothesis suggests that chromatin forms loops through the cohesin protein complex until reaching boundary elements. We develop an analytical theory for active loop extrusion that predicts loop formation probability and chromatin contact probabilities. Our model is validated with simulations and recapitulates experimental chromatin conformation capture data.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Brian Chan, Michael Rubinstein
Summary: The active loop extrusion hypothesis suggests that chromatin threads through the cohesin protein complex into progressively larger loops until reaching specific boundary elements. In this study, we develop an analytical theory for active loop extrusion which predicts the probability of loop formation as a nonmonotonic function and describes chromatin contact probabilities. Validation of our model using Monte Carlo and hybrid Molecular Dynamics-Monte Carlo simulations shows that our theory replicates experimental chromatin conformation capture data. Our results support active loop extrusion as a mechanism for chromatin organization and provide an analytical description of chromatin organization that can be utilized to specifically modify chromatin contact probabilities.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Polymer Science
Andrea Esposito, Alex Abraham, Mattia Conte, Francesca Vercellone, Antonella Prisco, Simona Bianco, Andrea M. Chiariello
Summary: Biophysical processes within cell nuclei play a crucial role in genome activities. Polymer physics models in synergy with numerical simulations are beneficial for studying various aspects of genome functions.
Article
Biology
Rakesh Das, Takahiro Sakaue, G. Shivashankar, Jacques Prost, Tetsuya Hiraiwa, Naama Barkai
Summary: This study constructs a polymer physics model based on the mechanistic scheme of Topoisomerase-II to investigate its effect on the spatial organization of interphase chromatin. The simulations show that Topoisomerase-II can phase separate chromatin into eu- and heterochromatic regions, with a wall-like organization of the euchromatic regions. The ability of the euchromatic regions to cross each other, induced by the enzymatic activity of Topoisomerase-II, leads to this phase separation. The model is extended to a bidisperse setting, and the characteristic features of enzymatic activity-driven phase separation are observed. These findings highlight the critical role of enzymatic activity in chromatin organization.
Article
Biochemistry & Molecular Biology
Amanda Souza Camara, Martin Mascher
Summary: The organisation of chromatin is crucial for cellular functions, but the mechanisms behind the formation of different chromatin regions are not yet well understood. Polymer models have been used to study these mechanisms, but further research is needed to consolidate the models.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Physics, Fluids & Plasmas
Mattia Conte, Luca Fiorillo, Carlo Annunziatella, Andrea Esposito, Francesco Musella, Alex Abraham, Simona Bianco, Andrea M. Chiariello
Summary: Novel technologies have revealed the complex three-dimensional organization of chromosomes within the cell nucleus, showing their functional purposes. Models and simulations have been used to quantitatively understand the scaling behavior of chromatin at the topologically associating domains level, validated against experimental observations.
Article
Biochemical Research Methods
Betul Akgol Oksuz, Liyan Yang, Sameer Abraham, Sergey V. Venev, Nils Krietenstein, Krishna Mohan Parsi, Hakan Ozadam, Marlies E. Oomen, Ankita Nand, Hui Mao, Ryan M. J. Genga, Rene Maehr, Oliver J. Rando, Leonid A. Mirny, Johan H. Gibcus, Job Dekker
Summary: Chromosome conformation capture assays, such as Hi-C and Micro-C, are used to map chromatin interactions and understand chromosome folding mechanisms. Through systematic evaluation of experimental parameters, an optimized Hi-C protocol was developed for detecting loops and compartments, improving the ability to study chromosome organization.
Article
Multidisciplinary Sciences
Barbara Scalvini, Helmut Schiessel, Anatoly Golovnev, Alireza Mashaghi
Summary: A toolbox for topological analysis based on Circuit Topology has been developed in this study, allowing for the quantification of inter- and intracellular genomic heterogeneity. The analysis of single-cell Hi-C data reveals highly conserved topological features that inform on the topological state of the nucleus and indicate the presence of active loop extrusion.
Article
Multidisciplinary Sciences
Luan Nguyen, Arne Van Hoeck, Edwin Cuppen
Summary: This study demonstrates the use of whole-genome DNA sequencing and a machine learning model called Cancer of Unknown Primary Location Resolver to classify metastatic tumors, improving diagnosis and treatment decision-making.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Monika Yadav, Manisha Jalan, Madhulika Srivastava
Summary: The intranuclear position of the TCRb locus is dynamically altered during thymic development and is influenced by the enhancer Eb. The ability to reposition the target locus relative to the chromosome territory highlights a novel aspect of enhancer activity, which may contribute to gene expression regulation. These observations have implications for understanding enhancer function in three-dimensional genome organization.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Oncology
Kosuke Yamaguchi, Xiaoying Chen, Asami Oji, Ichiro Hiratani, Pierre-Antoine Defossez
Summary: Chromatin changes in cancer have significant implications for gene expression, genome stability, and cancer progression, making them important for diagnosis and treatment.
Article
Biochemistry & Molecular Biology
Jacqueline Chyr, Zhigang Zhang, Xi Chen, Xiaobo Zhou
Summary: In this study, a machine-learning model called PredTAD was used to explore the relationship between multi-omics data and higher-order chromatin structures, leading to the discovery of the ability to predict boundary changes using simple data and identifying TAD boundary alterations involved in important signaling pathways and oncogene expression in the breast cancer genome.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Rahul Sureka, Akshay Kumar Avvaru, Divya Tej Sowpati, Rashmi Upadhyay Pathak, Rakesh Kumar Mishra
Summary: The nuclear matrix is a crucial nucleoskeleton in eukaryotic cells, and matrix attachment regions (MARs) play important roles in genomic organization and transcriptional regulation. This study reveals the dynamic changes of MARs during embryonic development and shows the significance of nuclear matrix organization and MARs dynamics in cell differentiation.
Article
Biology
Xiangyan Shi, Bhuvaneswari Kannaian, Chinmayi Prasanna, Aghil Soman, Lars Nordenskioeld
Summary: This study used solid-state NMR to investigate the structure and dynamics of histone H2B in the context of the nucleosome core particle, revealing its crucial role in chromatin biology. The researchers characterized the structure and dynamics of H2B in precipitated nucleosome core particles at a physiological concentration. They obtained detailed insights into the dynamic properties of H2B at different timescales and observed potential mechanisms by which H2B interacts with DNA to modulate its activities.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemical Research Methods
Kseniia Cheloshkina, Maria Poptsova
Summary: The study analyzed a large number of cancer breakpoints and identified that transcription and formation of non-B DNA structures are the major processes contributing to cancer genome fragility, with epigenetic factors also playing a role. Each cancer type has its own characteristics in breakpoint distribution, and predictive models for cancer breakpoint formation can be improved using machine learning approaches.
PLOS COMPUTATIONAL BIOLOGY
(2021)