Article
Cell Biology
Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R. Wasylishen
Summary: Daxx functions as a histone chaperone for the histone H3 variant H3.3 and is essential for embryonic development. It interacts with Atrx to deposit H3.3 into heterochromatin, and this interaction is dispensable for viability. However, the interaction between Daxx and H3.3 is essential for postnatal viability and is important for silencing endogenous retroviruses and maintaining proper immune cell composition.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Lia M. Pinto, Alexandros Pailas, Max Bondarchenko, Abhishek Bharadwaj Sharma, Katrin Neumann, Anthony J. Rizzo, Celine Jeanty, Nathalie Nicot, Carine Racca, Mindy K. Graham, Catherine Naughton, Yaqun Liu, Chun-Long Chen, Paul J. Meakin, Nick Gilbert, Sebastien Britton, Alan K. Meeker, Christopher M. Heaphy, Florence Larminat, Eric Van Dyck
Summary: Maintaining chromatin integrity at centromeres is crucial for preventing DNA breaks and genomic instability. The histone chaperone complex ATRX/DAXX is involved in establishing and maintaining centromeric chromatin structure. We discovered a novel ATRX-independent function for DAXX in promoting genome stability by preventing R-loop accumulation and DNA double-strand break formation at centromeres.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Michael McNicholas, Antonella De Cola, Zahedeh Bashardanesh, Amelia Foss, Cameron B. Lloyd, Steven Hebert, Damien Faury, Augusto Faria Andrade, Nada Jabado, Claudia L. Kleinman, Manav Pathania
Summary: Pediatric high-grade gliomas (pHGG) are heterogeneous brain tumors driven by clonal mutations in histone genes. We developed models representing 16 pHGG subtypes with different genetic alterations, which showed different treatment sensitivities and invasiveness. These models provide evidence for subtype-specific biology and therapeutic targeting in histone-mutant gliomas.
Article
Biology
Constance Kleijwegt, Florent Bressac, Coline Seurre, Wilhelm Bouchereau, Camille Cohen, Pascale Texier, Thomas Simonet, Laurent Schaeffer, Patrick Lomonte, Armelle Corpet
Summary: Promyelocytic leukemia nuclear bodies (PML NBs) play a crucial role in genome function by regulating the distribution of HIRA and histone dynamics. Additionally, they regulate the transcription of interferon-stimulated genes (ISGs) and H3.3 deposition mediated by HIRA during inflammatory response.
Article
Cell Biology
Roshan L. Shrestha, Vinutha Balachandra, Jee Hun Kim, Austin Rossi, Pranathi Vadlamani, Subhash Chandra Sethi, Laurent Ozbun, Shinjen Lin, Ken Chin -Chien Cheng, Raj Chari, Tatiana S. Karpova, Gianluca Pegoraro, Daniel R. Foltz, Natasha J. Caplen, Munira A. Basrai
Summary: Restricting CENP-A localization to centromeres prevents chromosomal instability. In this study, we identified CHAF1B and CHAF1A as factors that prevent mislocalization of CENP-A, and showed that DAXX promotes mislocalization of CENP-A in CHAF1B-depleted cells.
JOURNAL OF CELL SCIENCE
(2023)
Article
Oncology
Daniel Haag, Norman Mack, Patricia Benites Goncalves da Silva, Britta Statz, Jessica Clark, Koji Tanabe, Tanvi Sharma, Natalie Jaeger, David T. W. Jones, Daisuke Kawauchi, Marius Wernig, Stefan M. Pfister
Summary: The study found that the H3.3-K27M mutation has different effects on different neural cell types, with only neural stem cells capable of giving rise to tumors in an in vivo model by inducing H3.3-K27M and TP53 inactivation.
Article
Cell Biology
Chao-Pei Liu, Wenxing Jin, Jie Hu, Mingzhu Wang, Jingjing Chen, Guohong Li, Rui-Ming Xu
Summary: In this study, Liu et al. investigated how sNASP binds H3-H4 in the presence and absence of ASF1, two major histone H3-H4 chaperones found in distinct and common complexes, during chromosomal duplication. They show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded N alpha region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3-H4 complex, providing new mechanistic insights into coordinated histone binding and transfer by histone chaperones.
GENES & DEVELOPMENT
(2021)
Article
Pharmacology & Pharmacy
Peipei Wu, Su-Jiun Lin, Danqi Chen, Chunyuan Jin
Summary: Arsenic exposure is associated with increased cancer risk, and epigenetic mechanisms play a crucial role in arsenic-mediated carcinogenesis. Our study identifies the protein MCM2, a histone chaperone, as a key factor in the disruption of H3.3 deposition caused by the polyadenylation of H3.1 mRNA under conditions of arsenic exposure. Our findings suggest that changes in the interaction between MCM2 and H3.3, due to polyadenylation of H3.1 mRNA, may play a pivotal role in arsenic-induced carcinogenesis.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Yu Fu, Zhenglin Zhu, Geng Meng, Rijun Zhang, Yueping Zhang
Summary: Post-translational modifications of histone proteins play a crucial role in gene expression and cell fate decisions. Developing efficient methods for introducing mutations to histones is vital for studying these modifications. By utilizing a CRISPR-Cas9 based system in yeast cells, researchers successfully generated multiple histone mutants, presenting a valuable tool for the field of epigenetics.
SCIENTIFIC REPORTS
(2021)
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
Chemistry, Multidisciplinary
Sevastyan O. Rabdano, Matthew D. Shannon, Sergei A. Izmailov, Nicole Gonzalez Salguero, Mohamad Zandian, Rudra N. Purusottam, Michael G. Poirier, Nikolai R. Skrynnikov, Christopher P. Jaroniec
Summary: The positively charged N-terminal histone tails interact with nucleosomal DNA, influencing their susceptibility to modifications and recognition by chromatin-binding proteins. The NMR data reveals that H4 tails are dynamically disordered in nucleosomes, showing a reduced conformational flexibility compared to free peptides. The findings suggest a fuzzy interaction between histone H4 tails and nucleosomal DNA, characterized by variable salt bridges and hydrogen bonds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell & Tissue Engineering
Kosuke Funato, Ryan C. Smith, Yuhki Saito, Viviane Tabar
Summary: The study reveals that the H3.3G34R-mutant glioma model recapitulates key features of the tumors, showing specificity to forebrain interneuronal progenitors; Mutations in H3.3G34R, ATRX, and TP53 cooperatively impact RNA splicing events and lead to increased expression of components of the Notch pathway, particularly NOTCH2NL gene family.
Review
Cell Biology
Laura Prendergast, Danny Reinberg
Summary: Recent advances in chromatin and epigenetics research have highlighted the significance of core histones, histone variants, and their post-translational modifications in regulating chromatin structure. The role of linker histone H1, which was previously understudied, has come into focus due to its evolutionary conservation, variability in PTMs, and unique functions across different cell types. Contrary to previous assumptions, histone H1 variants are now recognized for their independent roles in various chromatin-based processes, challenging the traditional view of their function solely in chromatin compaction and transcriptional repression.
GENES & DEVELOPMENT
(2021)
Article
Reproductive Biology
Jaspreet K. Rishi, Kelsey Timme, Hunter E. White, Karl C. Kerns, Aileen F. Keating
Summary: This study found that DMBA exposure can alter histones and histone variants in the ovaries, and the responsivity is more pronounced in obesity, potentially impacting ovarian transcriptional regulation.
BIOLOGY OF REPRODUCTION
(2023)
Article
Oncology
Evangeline R. Jackson, Ryan J. Duchatel, Dilana E. Staudt, Mika L. Persson, Abdul Mannan, Sridevi Yadavilli, Sarah Parackal, Shaye Game, Wai Chin Chong, W. Samantha N. Jayasekara, Marion Le Grand, Padraic S. Kearney, Alicia M. Douglas, Izac J. Findlay, Zacary P. Germon, Holly P. McEwen, Tyrone S. Beitaki, Adjanie Patabendige, David A. Skerrett-Byrne, Brett Nixon, Nathan D. Smith, Bryan Day, Neevika Manoharan, Sumanth Nagabushan, Jordan R. Hansford, Dinisha Govender, Geoff B. McCowage, Ron Firestein, Meegan Howlett, Raelene Endersby, Nicholas G. Gottardo, Frank Alvaro, Sebastian M. Waszak, Martin R. Larsen, Yolanda Colino-Sanguino, Fatima Valdes-Mora, Andria Rakotomalala, Samuel Meignan, Eddy Pasquier, Nicolas Andre, Esther Hulleman, David D. Eisenstat, Nicholas A. Vitanza, Javad Nazarian, Carl Koschmann, Sabine Mueller, Jason E. Cain, Matthew D. Dun
Summary: Diffuse midline gliomas are highly lethal childhood cancers. Palliative radiotherapy is the only established treatment with limited survival benefits. ONC201, a combination of a DRD2 antagonist and ClpP agonist, has shown promising preclinical and emerging clinical efficacy in treating diffuse intrinsic pontine gliomas. Further research is needed to understand the mechanisms of response, the impact of recurring genomic features, and the potential combination therapy with a brain penetrant PI3K/Akt inhibitor, paxalisib.
Article
Cell Biology
Andrea Bjorkman, Soren L. Johansen, Lin Lin, Mike Schertzer, Dimitris C. Kanellis, Anna-Maria Katsori, Soren T. Christensen, Yonglun Luo, Jens S. Andersen, Simon J. Elsasser, Arturo Londono-Vallejo, Jiri Bartek, Kenneth B. Schou
GENES & DEVELOPMENT
(2020)
Article
Cell Biology
Birthe Meineke, Johannes Heimgertner, Juergen Eirich, Michael Landreh, Simon J. Elsasser
Article
Multidisciplinary Sciences
Carmen Navarro, Jing Lyu, Anna-Maria Katsori, Rozina Caridha, Simon J. Elsasser
NATURE COMMUNICATIONS
(2020)
Article
Biology
Milica Pesic, Dilfuza Egamberdieva, Bart Kolodziejczyk, Simon J. Elsasser, Vidushi S. Neergheen, Alexander Kagansky
Summary: The paper highlights the importance of biodiversity for sustainable development, human health, and well-being, urging policy makers to take innovative measures to prevent the accelerated loss of global biodiversity. It also emphasizes the key role of social and natural sciences in forming policies related to biodiversity, conservation, and health management.
Correction
Biology
Milica Pesic, Dilfuza Egamberdieva, Bartlomiej Kolodziejczyk, Simon J. Elsaesser, Vidushi S. Neergheen, Alexander Kagansky
Summary: The third author's name was incomplete in the initial online publication.
Article
Multidisciplinary Sciences
Alisa Alekseenko, Donal Barrett, Yerma Pareja-Sanchez, Rebecca J. Howard, Emilia Strandback, Henry Ampah-Korsah, Urska Rovsnik, Silvia Zuniga-Veliz, Alexander Klenov, Jayshna Malloo, Shenglong Ye, Xiyang Liu, Bjorn Reinius, Simon J. Elsasser, Tomas Nyman, Gustaf Sandh, Xiushan Yin, Vicent Pelechano
Summary: The study optimized the RT-LAMP detection method to make it more cost-effective and applicable for expanding the scale of COVID-19 diagnostics; it explored the compatibility between different DNA polymerases and reverse transcriptases, and validated the effectiveness of the method in clinical samples; the optimized RT-LAMP method is expected to facilitate the global expansion of SARS-CoV-2 testing, particularly in places where commercial alternatives cannot meet the demand.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Dorte Schlesinger, Simon J. Elsasser
Summary: Short ORFs (sORFs), which contain a start and stop codon within 100 codons, can be found in organisms across all domains of life and often outnumber annotated protein-coding ORFs. Recent advancements in technology have led to the identification of thousands of potential coding sORFs, shedding light on the overlooked coding potential of these small proteins. The emerging field of microproteins in eukaryotes shows promise for uncovering new functional small proteins encoded in the genome.
Article
Biochemistry & Molecular Biology
Lea S. van Husen, Anna-Maria Katsori, Birthe Meineke, Lars O. Tjernberg, Sophia Schedin-Weiss, Simon J. Elsasser
Summary: The use of hiPSC technology has transformed studies on human biology by allowing derivation of various cell types and tissue models to study complex diseases. Engineered hiPSCs have shown potential for site-specific incorporation of non-canonical amino acids, which can be used for labeling and further modifications. This technology is expected to open up a wide range of applications in protein research in brain organoids and other hiPSC-derived tissue models.
Article
Multidisciplinary Sciences
Niclas Roxhed, Annika Bendes, Matilda Dale, Cecilia Mattsson, Leo Hanke, Tea Dodig-Crnkovic, Murray Christian, Birthe Meineke, Simon Elsasser, Juni Andrell, Sebastian Havervall, Charlotte Thalin, Carina Eklund, Joakim Dillner, Olof Beck, Cecilia E. Thomas, Gerald McInerney, Mun-Gwan Hong, Ben Murrell, Claudia Fredolini, Jochen M. Schwenk
Summary: Researchers have developed a multiplexed approach to screen IgG and IgM levels against several SARS-CoV-2 proteins in home-sampled dried blood spots and estimated a seroprevalence of 12.5% in Stockholm in spring of 2020.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Dimitris C. Kanellis, Jaime A. Espinoza, Asimina Zisi, Elpidoforos Sakkas, Jirina Bartkova, Anna-Maria Katsori, Johan Bostrom, Lars Dyrskjot, Helle Broholm, Mikael Altun, Simon J. Elsasser, Mikael S. Lindstrom, Jiri Bartek
Summary: eIF4A3 plays a role in ribosome biogenesis and p53 regulation, with its depletion leading to cell cycle arrest and changes in cell death regulation pathways. The expression and subnuclear localization of eIF4A3 among clinical cancer specimens correlate with RiBi status, impacting cancer pathogenesis and treatment.
Article
Biochemistry & Molecular Biology
Rui Shao, Banushree Kumar, Katja Lidschreiber, Michael Lidschreiber, Patrick Cramer, Simon J. Elsasser
Summary: This study uses transient transcriptome sequencing and RNA polymerase II occupancy profiling to investigate the pluripotent states of mouse embryonic stem cells. It reveals that RNA synthesis and turnover rates are globally reduced in the ground and paused states, accompanied by a decrease in polymerase elongation velocity and alterations in the Pol II termination window. The findings suggest that transcription activity plays a crucial role in determining mRNA levels, and changes in transcription kinetics lead to different pluripotent states.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jing Lyu, Rui Shao, Philip Yuk Kwong Yung, Simon J. Elsasser
Summary: Recent evidence suggests that G-quadruplex (G4) structures impact gene expression, DNA methylation, replicative processes, and genome stability. The use of CUT&Tag technology allows high-resolution mapping of G4 structures in mammalian cells, revealing widespread presence at active promoters and enhancers in mouse ESCs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jorge Garcia Morato, Friederike Hans, Felix von Zweydorf, Regina Feederle, Simon J. Elsasser, Angelos A. Skodras, Christian Johannes Gloeckner, Emanuele Buratti, Manuela Neumann, Philipp J. Kahle
Summary: TDP-43 is a nucleic acid binding protein that plays a role in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Post-translational modifications and acetylation of TDP-43 affect its interaction with RNA and its cellular localization. This study found that different lysine acetylations of TDP-43 modulate its nuclear import, RNA binding, and phase separation, suggesting regulatory mechanisms for TDP-43 pathogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Lorenzo Lafranchi, Dorte Schlesinger, Kyle J. Kimler, Simon J. Elsasser
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Multidisciplinary Sciences
Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C. L. Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. McConechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski
NATURE COMMUNICATIONS
(2019)
