Review
Cell Biology
Lin Li, Qiang Yuan, Yue-Ming Chu, Hang-Yu Jiang, Ju-Hua Zhao, Qiang Su, Dan-Qun Huo, Xiao-Fen Zhang
Summary: HJURP gene plays an important role in tumor cells and is associated with tumor proliferation, invasion, metastasis, and immune response. The study on the functional and molecular mechanisms of HJURP provides new targets for future cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Julio C. Flores C. Servin, Rachel R. Brown, Aaron F. Straight
Summary: Flores Servin, Brown, and Straight discovered that vertebrate CENP-A assembly is restricted to G1 phase due to the inhibitory activities of HJURP phosphorylation and M18BP1.S competitive binding to CENP-C. These inhibitory activities prevent the metaphase centromere localization of HJURP and thus hinder CENP-A assembly. Removal of these inhibitory activities allows CENP-A assembly in metaphase.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Qianhua Dong, Xue-lei Liu, Xiao-hui Wang, Yu Zhao, Yu-hang Chen, Fei Li
Summary: CENP-T interacts with Ccp1 to regulate centromere binding throughout the cell cycle, involving phosphorylation of a specific domain CIM. Competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis, uncovering a previously unrecognized mechanism for kinetochore assembly through the cell cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Liqiao Hu, Congcong Zhao, Mingjie Liu, Shuaiyu Liu, Jingjing Ye, Kehui Wang, Jinyun Shi, Wei Tian, Xiaojing He
Summary: CENP-I directly interacts with centromeric DNA and stabilizes the deposition of CENP-A. The DNA binding of CENP-I is crucial for the loading of CENP-A and the localization of centromeres.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Megan A. Mahlke, Lior Lumerman, Peter Ly, Yael Nechemia-Arbely
Summary: Centromere identity is defined and maintained by CENP-A, but how its positioning and maintenance during DNA replication are accomplished remains unclear. The newly released T2T genome assembly provides a valuable tool for studying CENP-A positioning. Mapping CENP-A position to the T2T assembly revealed consistent localization after cell divisions, while variations in CENP-A expression were observed across different human cell lines. Despite CENP-A dilution during DNA replication, it is reliably reloaded onto the same sequences in daughter centromeres, preserving centromere identity in human cells.
LIFE SCIENCE ALLIANCE
(2023)
Review
Biochemistry & Molecular Biology
Harsh Nagpal, Beat Fierz
Summary: The centromere is an indispensable chromatin domain in eukaryotes, necessary for chromosome segregation; its unique structure relies on nucleosomes containing CENP-A; CENP-A binding proteins play a crucial role in modulating the structure of centromeric chromatin.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ye Li, Qing Yi, Xiaoli Liao, Chenglong Han, Li Zheng, Hui Li, Qian Yu, Xuexin Yan, Xinyu Chen, Huawei Zhu, Bi Zhao, Qiulu Lin, Li Liang, Li Wang, Fanghui Qin, Weimin Xie, Yongqiang Li, Wenfeng Huang
Summary: HJURP is identified as a crucial oncogene promoting HCC progression, with its high expression significantly associated with patient survival. HJURP enhances tumorigenesis through reducing cell arrest and increasing invasiveness in HCC.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cell Biology
Kousik Sundararajan, Aaron F. Straight
Summary: Eukaryotes segregate their chromosomes during mitosis and meiosis by attaching them to the microtubules of the spindle using centromeres, with CENP-A playing a crucial role in centromere organization. Understanding and correcting errors in CENP-A organization is important for proper chromosome segregation during cell division.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Koei Okazaki, Megumi Nakano, Jun-ichirou Ohzeki, Koichiro Otake, Kazuto Kugou, Vladimir Larionov, William C. Earnshaw, Hiroshi Masumoto
Summary: Human artificial chromosomes (HACs) are formed by introducing large centromeric sequences into cells, and the balance of chromatin states on the alphoid DNA is crucial for HAC formation. Our study explores the relationship between chromatin architecture and de novo HAC formation efficiency, and found that a combination of mutated and wild-type alphoid repeats enhances HAC formation.
Article
Oncology
Yunlu Jia, Jianbiao Zhou, Tze King Tan, Tae-Hoon Chung, Yongxia Chen, Jing-Yuan Chooi, Takaomi Sanda, Melissa J. Fullwood, Sinan Xiong, Sabrina H. M. Toh, Kalpnaa Balan, Regina W. J. Wong, Julia S. L. Lim, Enfan Zhang, Zhen Cai, Peng Shen, Wee Joo Chng
Summary: The presence of super-enhancers in t(4;14) translocated multiple myeloma promotes the expression of HJURP through histone modification and transcriptional activation, leading to cell proliferation and apoptosis. This study introduces an efficient approach, SE profiling, to identify new targets and understand molecular pathogenesis in specific subtypes of cancer.
Article
Oncology
Yuyang Zhang, Wei Zhang, Lili Sun, Yuanyuan Yue, Dan Shen, Bingbing Tian, Meng Du, Meicen Dong, Yang Liu, Dan Zhang
Summary: This study reveals that high expression of HJURP in ovarian cancer is associated with inhibited cell proliferation and altered cell cycle and mitochondrial content. HJURP is positively correlated with CENP-A and plays a significant role in regulating the growth of ovarian cancer cells through targeting CENP-A.
BULLETIN DU CANCER
(2022)
Review
Cell Biology
Charlene Renaud-Pageot, Jean-Pierre Quivy, Marina Lochhead, Genevieve Almouzni
Summary: CENP-A plays a critical role in chromosome segregation and genome integrity maintenance in mammals, but its overexpression is linked to cancer development. Studies have shown that CENP-A overexpression can affect genome integrity, cell fate, and nuclear organization in cancer, highlighting its potential as a target for cancer treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yaqian Li, Jiabin Wang, Xuecheng Chen, Daniel M. Czajkowsky, Zhifeng Shao
Summary: This study used super-resolution optical microscopy to examine the amount of CENP-A and DNA in human centromeric chromatin. The researchers found that the amount of CENP-A remains unchanged in different sized domains, suggesting a strict relationship between CENP-A and microtubule stoichiometries. Additionally, the study revealed that the CENP-A centromeric domain is primarily composed of CENP-A nucleosomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Georgia Levidou, Konstantinos Palamaris, Alexandros G. Sykaras, Georgios Andreadakis, Christos Masaoutis, Irene Theochari, Penelope Korkolopoulou, Dimitra Rontogianni, Stamatios Theocharis
Summary: This study reveals a significant interaction between CENP-A and HJURP in thymic epithelial tumors (TETs). Furthermore, the cytoplasmic immunostaining pattern of CENP-A may have a favorable prognostic value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Catalina Salinas-Luypaert, Praveen Kumar Allu, Glennis A. Logsdon, Jennine M. Dawicki-McKenna, Craig W. Gambogi, Daniele Fachinetti, Ben E. Black
Summary: Functional tags are widely used in cell biology, with the centromere being a particularly useful locus for such studies. Regulation of centromere function involves posttranslational modification of key components, including CENP-A. Some have questioned the effectiveness of functional tags in studying the essentiality of specific posttranslational modifications, such as CENP-A(K124) ubiquitination.
Article
Multidisciplinary Sciences
David Sitbon, Ekaterina Boyarchuk, Florent Dingli, Damarys Loew, Genevieve Almouzni
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Roman M. Chabanon, Daphne Morel, Thomas Eychenne, Leo Colmet-Daage, Ilirjana Bajrami, Nicolas Dorvault, Marlene Garrido, Cornelia Meisenberg, Andrew Lamb, Carine Ngo, Suzanna R. Hopkins, Theodoros Roumeliotis, Samuel Jouny, Clemence Henon, Asuka Kawai-Kawachi, Clemence Astier, Asha Konde, Elaine Del Nery, Christophe Massard, Stephen J. Pettitt, Raphael Margueron, Jyoti S. Choudhary, Genevieve Almouzni, Jean-Charles Soria, Eric Deutsch, Jessica A. Downs, Christopher J. Lord, Sophie Postel-Vinay
Summary: Inactivation of PBRM1 is common in cancer, including ccRCC. Studies show that PARP and ATR inhibitors are synthetic lethal with PBRM1 deficiency, providing a basis for using these inhibitors in PBRM1-defective cancers.
Correction
Multidisciplinary Sciences
Nikolaus Rajewsky, Genevieve Almouzni, Stanislaw A. Gorski, Stein Aerts, Ido Amit, Michela G. Bertero, Christoph Bock, Annelien L. Bredenoord, Giacomo Cavalli, Susanna Chiocca, Hans Clevers, Bart De Strooper, Angelika Eggert, Jan Ellenberg, Xose M. Fernandez, Marek Figlerowicz, Susan M. Gasser, Norbert Hubner, Jorgen Kjems, Jurgen A. Knoblich, Grietje Krabbe, Peter Lichter, Sten Linnarsson, Jean-Christophe Marine, John C. Marioni, Marc A. Marti-Renom, Mihai G. Netea, Dorthe Nickel, Marcelo Nollmann, Halina R. Novak, Helen Parkinson, Stefano Piccolo, Ines Pinheiro, Ana Pombo, Christian Popp, Wolf Reik, Sergio Roman-Roman, Philip Rosenstiel, Joachim L. Schultze, Oliver Stegle, Amos Tanay, Giuseppe Testa, Dimitris Thanos, Fabian J. Theis, Maria-Elena Torres-Padilla, Alfonso Valencia, Celine Vallot, Alexander van Oudenaarden, Marie Vidal, Thierry Voet
Article
Biology
Daniel Jeffery, Alberto Gatto, Katrina Podsypanina, Charlene Renaud-Pageot, Rebeca Ponce Landete, Lorraine Bonneville, Marie Dumont, Daniele Fachinetti, Genevieve Almouzni
Summary: The study establishes an inducible and reversible CENP-A overexpression system, combined with a switch in p53 status in human cell lines, revealing p53 as a key determinant of how CENP-A impacts cell state, cell identity, and therapeutic response. The findings show that CENP-A overexpression promotes senescence and radiosensitivity when p53 is functional, while promoting epithelial-mesenchymal transition when p53 is inactivated.
COMMUNICATIONS BIOLOGY
(2021)
Editorial Material
Genetics & Heredity
Ines Pinheiro, Maria-Elena Torres-Padilla, Genevieve Almouzni
Article
Oncology
Pierre Verrelle, Didier Meseure, Frederique Berger, Audrey Forest, Renaud Leclere, Andre Nicolas, Emilie Fortas, Xavier Sastre-Garau, Marick Lae, Sabah Boudjemaa, Rodrigue Mbagui, Valentin Calugaru, Dalila Labiod, Leanne De Koning, Genevieve Almouzni, Jean-Pierre Quivy
Summary: The subnuclear distribution of CENP-A serves as an independent predictive marker for local disease control and curability by chemoradiation therapy in locally advanced head and neck squamous cell cancer patients, providing a reliable marker for precision medicine. This study highlights the potential clinical applicability of CENP-A labeling as a cost-effective marker compatible with clinical time constraints during therapy.
Article
Genetics & Heredity
Daniela Torres-Campana, Beatrice Horard, Sandrine Denaud, Gerard Benoit, Benjamin Loppin, Guillermo A. Orsi
Summary: This study identifies regulators and mechanisms involved in the expression of the dhd gene, shedding light on the complex regulation of gene expression in multicellular development. The researchers demonstrate the critical role of multiple epigenomic effectors in tissue-specific gene activation.
Article
Biochemistry & Molecular Biology
Alberto Gatto, Audrey Forest, Jean-Pierre Quivy, Genevieve Almouzni
Summary: This study reveals the dual deposition mode of histone variants H3.1 and H3.3 in human cells during S phase, which ensures a stable marking with H3.3 flanked on both sides by H3.1. The H3.1/H3.3 boundaries correspond to the initiation zones of early origins, and the HIRA-dependent deposition of H3.3 plays a crucial role in preserving these boundaries and contributing to the chromatin-based definition of early replication zones.
Article
Cell Biology
Saul Carcamo, Christie B. Nguyen, Elena Grossi, Dan Filipescu, Aktan Alpsoy, Alisha Dhiman, Dan Sun, Sonali Narang, Jochen Imig, Tiphaine C. Martin, Ramon Parsons, Iannis Aifantis, Aristotelis Tsirigos, Julio A. Aguirre-Ghiso, Emily C. Dykhuizen, Dan Hasson, Emily Bernstein
Summary: ARID2 is the most commonly mutated member of the SWI/SNF complex in melanoma. Its deficiency leads to defective assembly of the PBAF complex and redistribution of the BAF complex. ARID2 depletion results in reduced chromatin accessibility and gene expression in certain regions, while enhancers occupied by the BAF complex gain accessibility and gene expression related to invasion. The occupancy of melanoma-relevant transcription factors is affected by altered accessibility, and correlates significantly with the observed transcriptional changes. Furthermore, ARID2-deficient cells acquire the ability to colonize distal organs in multiple animal models.
Article
Multidisciplinary Sciences
Dan Sun, Deepak K. Singh, Saul Carcamo, Dan Filipescu, Bassem Khalil, Xin Huang, Brett A. Miles, William Westra, Karl Christoph Sproll, Dan Hasson, Emily Bernstein, Julio A. Aguirre-Ghiso
Summary: MacroH2A variants play a crucial role in inhibiting metastasis in cancer. Dormant disseminated cancer cells (DCCs) were found to have increased levels of macroH2A variants compared to proliferating primary or metastatic lesions in head and neck squamous cell carcinoma. The study further reveals that transforming growth factor-beta 2 and p38 alpha/0 pathways up-regulate macroH2A expression, leading to DCC dormancy and suppression of metastasis in vivo.
Review
Biochemistry & Molecular Biology
Jeanne Rakotopare, Franck Toledo, Alfonso Baldi
Summary: Studies on both animal models and humans have revealed that mutations affecting p53 activity can lead to features of certain bone marrow failure syndromes, including dyskeratosis congenita, Diamond-Blackfan anemia, and Fanconi anemia. p53 regulates multiple genes related to these syndromes, forming a positive feedback loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Dan Filipescu, Saul Carcamo, Aman Agarwal, Navpreet Tung, Etienne Humblin, Matthew S. Goldberg, Nikki S. Vyas, Kristin G. Beaumont, Deniz Demircioglu, Subhasree Sridhar, Flavia G. Ghiraldini, Claudia Capparelli, Andrew E. Aplin, Helene Salmon, Robert Sebra, Alice O. Kamphorst, Miriam Merad, Dan Hasson, Emily Bernstein
Summary: Filipescu et al. demonstrate that MacroH2A deficiency in cancer-associated fibroblasts leads to altered chromatin looping and elevated inflammatory gene expression, resulting in impaired immune cell function and reduced anti-tumour response in melanoma. This study highlights the tumour suppressive role of MacroH2A variants in regulating chromatin architecture in the tumour stroma, with potential implications for human melanoma.
NATURE CELL BIOLOGY
(2023)
Meeting Abstract
Oncology
Etienne Humblin, Verena Van der Heide, Dan Filipescu, Ashley Lu, Alessandra Soares-Schanoski, Myvizhi Selvan, Laila Horta, Zeynep Gumus, Emily Bernstein, Jerry Chipuk, Dirk Homann, Alice O. Kamphorst
Meeting Abstract
Immunology
Etienne Humblin, Verena Van der Heide, Dan Filipescu, Ashley Lu, Myvizhi Selvan, Zeynep Gumus, Emily Bernstein, Jerry Chipuk, Dirk Homann, Alice O. Kamphorst
JOURNAL OF IMMUNOLOGY
(2022)
Review
Oncology
Flavia G. Ghiraldini, Dan Filipescu, Emily Bernstein
Summary: Cancer is a complex disease characterized by loss of cellular homeostasis due to genetic and epigenetic alterations. Histone variants play critical roles in processes like maintenance of genome integrity, nuclear architecture, and cell identity. Cancer cells hijack histone variants and their chaperones to disrupt homeostasis, which is emerging as a common strategy across various cancers, especially solid tumors.
NATURE REVIEWS CANCER
(2021)