Review
Genetics & Heredity
Michael Chiang, Chris A. Brackley, Davide Marenduzzo, Nick Gilbert
Summary: Fitting-free mechanistic models based on polymer simulations predict chromatin folding in 3D by focussing on the underlying biophysical mechanisms. This class of models has been increasingly used in conjunction with experiments to study the spatial organisation of eukaryotic chromosomes. Feedback from experiments to models leads to successive model refinement and has previously led to the discovery of new principles for genome organisation.
TRENDS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Catarina Rosa, Parul Singh, Patty Chen, Ameya Sinha, Aurelie Claes, Peter R. Preiser, Peter C. Dedon, Sebastian Baumgarten, Artur Scherf, Jessica M. Bryant
Summary: The complex life cycle of the malaria parasite Plasmodium falciparum is driven by specific transcriptional programs, but the mechanisms behind gene activation or silencing at specific times are unclear. In this study, researchers investigated the role of the cohesin subunit SMC3 in P. falciparum. They found that knockdown of SMC3 during the early stages of the parasite's life cycle resulted in the upregulation of certain genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq analyses revealed that SMC3 binding at the promoter regions of these genes correlated with gene repression and chromatin accessibility during the parasite life cycle.
Article
Biochemistry & Molecular Biology
Antonina Hafner, Minhee Park, Scott E. Berger, Sedona E. Murphy, Elphege P. Nora, Alistair N. Boettiger
Summary: Population-level analyses have shown the significant roles of CTCF and cohesin in mammalian genome organization. However, their contributions at the single-cell level were not fully understood until now. This study used super-resolution microscopy to explore the effects of CTCF and cohesin removal, revealing their distinct contributions to loop stacking and the organization of the genome at the single-cell level.
Article
Biochemistry & Molecular Biology
Dingdang Yu, Guoyu Chen, Yuci Wang, Yining Wang, Risheng Lin, Nanbo Liu, Ping Zhu, Hang Liu, Tao Hu, Rui Feng, Haizhong Feng, Fei Lan, Jiabin Cai, Hao Chen
Summary: PDS5A and PDS5B proteins co-localize with RAD21 and CTCF at loop anchors, playing important roles in the formation and size regulation of chromatin loops. Rapid degradation of PDS5A or PDS5B in liver cancer cells results in reduced chromatin loops and increased loop size. PDS5B loss has a stronger impact on RAD21 and CTCF signals at loop anchors compared to PDS5A.
Article
Multidisciplinary Sciences
Ester Marina-Zarate, Ana Rodriguez-Ronchel, Manuel J. Gomez, Fatima Sanchez-Cabo, Almudena R. Ramiro
Summary: CTCF is a DNA-binding protein that plays important roles in chromatin structure organization and transcriptional regulation; however, the functional determinants of different CTCF-binding sites (CBS) are not well characterized. Using a conditional mouse model, we identified a set of CBSs that are lost upon CTCF depletion (lost CBSs) and another set that persists (retained CBSs). Retained CBSs are more similar to the consensus CTCF-binding sequence and usually span tandem CTCF peaks. Lost CBSs are enriched at enhancers and promoters and associated with active chromatin marks and higher transcriptional activity. In contrast, retained CBSs are enriched at TAD and loop boundaries, acting as chromatin barriers between distinct chromatin states.
Article
Biotechnology & Applied Microbiology
Megan Justice, Audra F. Bryan, Juanita C. Limas, Jeanette Gowen Cook, Jill M. Dowen
Summary: The study found that loss of WIZ leads to changes in cohesin localization on chromatin, distinct from loss of G9a and canonical cohesin unloading factor WAPL. Ectopic cohesin binding sites were observed after the loss of WIZ, enriched for activating histone modifications and transcription factor motifs. WIZ appears to function independently of its previously identified role in heterochromatin formation.
Article
Cell Biology
Ryotaro Kawasumi, Takuya Abe, Ivan Psakhye, Keiji Miyata, Kouji Hirota, Dana Branzei
Summary: The study reveals the collaborative role of vertebrate CTF18 and DDX11 in providing sufficient amounts of chromatin-loaded cohesin for sister chromatid cohesion generation in the presence of WAPL-mediated cohesin unloading activity, modulating chromosome structure and being essential for cellular proliferation in vertebrates.
GENES & DEVELOPMENT
(2021)
Article
Biology
Lesly Calderon, Felix D. Weiss, Jonathan A. Beagan, Marta S. Oliveira, Radina Georgieva, Yi-Fang Wang, Thomas S. Carroll, Gopuraja Dharmalingam, Wanfeng Gong, Kyoko Tossell, Vincenzo de Paola, Chad Whilding, Mark A. Ungless, Amanda G. Fisher, Jennifer E. Phillips-Cremins, Matthias Merkenschlager
Summary: Cohesin plays a significant role in the expression of genes involved in neuronal maturation and homeostasis. Different classes of activity-regulated genes in mouse primary cortical neurons have distinct reliance on cohesin. Cohesin is required for full expression of certain secondary response genes with long-range chromatin contacts and also scales with the genomic distance traversed by chromatin loops.
Review
Virology
Lisa Beatrice Caruso, Davide Maestri, Italo Tempera
Summary: Epstein-Barr Virus (EBV) is a widely distributed human gamma-herpesvirus. It is responsible for about 200,000 cancer cases per year. EBV can infect both B cells and epithelial cells. After entering the nucleus, the viral DNA undergoes circularization and chromatinization, establishing a lifelong latent infection. Different types of latency are characterized by different expressions of latent viral genes and the three-dimensional architecture of the viral genome. Various factors, such as CTCF, PARP1, MYC, and Nuclear Lamina, play a central role in the regulation and maintenance of this three-dimensional organization, emphasizing its importance in latency maintenance.
Article
Multidisciplinary Sciences
Wang Xi, Michael A. Beer
Summary: CTCF plays a critical role in three-dimensional chromatin looping interactions, with the specificity of CTCF binding events forming loops being difficult to predict. Competition and extrusion are key determinants of loop specificity.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Abhishek Agarwal, Sevastianos Korsak, Ashutosh Choudhury, Dariusz Plewczynski
Summary: Recent advances in genomic and imaging techniques have revealed the complex manner of organizing DNA, particularly the role of SMC proteins and cohesin complex in forming higher-order chromatin structures. Cohesin plays a fundamental role in chromatin organization and gene expression. This review discusses the dynamic nature of the cohesin-DNA complex, its importance in genome maintenance, and the methods used to study Cohesin-centered interactions.
Review
Genetics & Heredity
Jamie Phipps, Karine Dubrana
Summary: DNA double-strand breaks (DSBs) are a harmful form of DNA damage that require robust repair mechanisms. The repair process is influenced by chromatin composition and dynamics, as well as 3D genome organization and break localization. The cohesin complex, involved in chromosome folding and sister chromatid cohesion, is emerging as a key player in DNA damage response, affecting repair pathway choice and efficiency.
Article
Genetics & Heredity
Shu Zhang, Nadine Uebelmesser, Mariano Barbieri, Argyris Papantonis
Summary: High-resolution Micro-C is used to study the effect of RNA polymerase II (RNAPII) loss on chromosome looping. The formation of enhancer-promoter loops depends on RNAPII binding to their anchors. RNAPII plays a role in transcription as well as in setting up regulatory three-dimensional chromatin contacts, including cohesin loop extrusion.
Article
Cell Biology
Yina Zhu, Matthew Denholtz, Hanbin Lu, Cornelis Murre
Summary: The study demonstrates that calcium influx in activated neutrophils rapidly recruits NIPBL to active enhancers and promoters, leading to widespread changes in chromatin folding. The recruitment of NIPBL to enhancers is coordinated with P300, BRG1 and RNA polymerase II occupancy, while its binding to promoters is primarily associated with GC-rich DNA sequences.
GENES & DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Shubhra Ashish Bhattacharya, Eve Dias, Andrea Nieto-Aliseda, Marcus Buschbeck
Summary: This article investigates the significance of recurrent somatic mutations in genes encoding the chromatin-regulatory cohesin complex and its modulators in human malignancies, focusing on the high frequency mutation in the STAG2 gene in myeloid neoplasms. The article discusses the implications of STAG2 loss of function mutations, which are not associated with chromosomal aneuploidies or genomic instability, and summarizes the current knowledge on affected genes and pathways. Potential strategies for targeting cohesion-deficient disease cells are also discussed.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Cell Biology
Preksha Gupta, Thais Lavagnolli, Hegias Mira-Bontenbal, Amanda G. Fisher, Matthias Merkenschlager
Article
Cell Biology
Thais Lavagnolli, Preksha Gupta, Eva Hoermanseder, Hegias Mira-Bontenbal, Gopuraja Dharmalingam, Thomas Carroll, John B. Gurdon, Amanda G. Fisher, Matthias Merkenschlager
GENES & DEVELOPMENT
(2015)
Article
Biochemistry & Molecular Biology
Elizabeth Ing-Simmons, Vlad C. Seitan, Andre J. Faure, Paul Flicek, Thomas Carroll, Job Dekker, Amanda G. Fisher, Boris Lenhard, Matthias Merkenschlager
Review
Genetics & Heredity
Matthias Merkenschlager, Elphege P. Nora
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 17
(2016)
Editorial Material
Biochemistry & Molecular Biology
Elizabeth Ing-Simmons, Matthias Merkenschlager
TRENDS IN MOLECULAR MEDICINE
(2016)
Article
Multidisciplinary Sciences
Irene Cantone, Hakan Bagci, Dirk Dormann, Gopuraja Dharmalingam, Tatyana Nesterova, Neil Brockdorff, Claire Rougeulle, Celine Vallot, Edith Heard, Ronan Chaligne, Matthias Merkenschlager, Amanda G. Fisher
NATURE COMMUNICATIONS
(2016)
Article
Oncology
Jonathan Bond, Renae Domaschenz, Monica Roman-Trufero, Pierangela Sabbattini, Isabel Ferreiros-Vidal, Gareth Gerrard, Vahid Asnafi, Elizabeth Macintyre, Matthias Merkenschlager, Niall Dillon
Article
Cell & Tissue Engineering
Bryony Graham, Antoine Marcais, Gopuraja Dharmalingam, Thomas Carroll, Chryssa Kanellopoulou, Johannes Graumann, Tatyana B. Nesterova, Anna Bermange, Pijus Brazauskas, Barbara Xella, Skirmantas Kriaucionis, Douglas R. Higgs, Neil Brockdorff, Matthias Mann, Amanda G. Fisher, Matthias Merkenschlager
Article
Biology
Ziwei Liang, Karen E. Brown, Thomas Carroll, Benjamin Taylor, Isabel Ferreiros Vidal, Brian Hendrich, David Rueda, Amanda G. Fisher, Matthias Merkenschlager
Article
Biology
Aminah T. Ali, Lena Boehme, Guillermo Carbajosa, Vlad C. Seitan, Kerrin S. Small, Alan Hodgkinson
Article
Biochemical Research Methods
Camden Jansen, Ricardo N. Ramirez, Nicole C. El-Ali, David Gomez-Cabrero, Jesper Tegner, Matthias Merkenschlager, Ana Conesa, Ali Mortazavi
PLOS COMPUTATIONAL BIOLOGY
(2019)
Article
Biology
Maria Rojec, Antoine Hocher, Kathryn M. Stevens, Matthias Merkenschlager, Tobias Warnecke
Biographical-Item
Immunology
Amanda G. G. Fisher, Matthias Merkenschlager
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
Brooke C. Wilson, Lena Boehme, Ambra Annibali, Alan Hodgkinson, Thomas S. Carroll, Rebecca J. Oakey, Vlad C. Seitan
NATURE COMMUNICATIONS
(2020)
