Article
Microbiology
Youbao Zhao, Xiaorong Lin
Summary: The transcription factor Pas2 was found to be a key regulator in metabolic response to hypoxia in the human fungal pathogen Cryptococcus neoformans, interacting with another transcription factor Rds2. The Pas2/Rds2 complex plays a critical role in rewiring metabolism between respiration and fermentation, shedding light on the adaptation mechanisms of lower eukaryotes like C. neoformans to low oxygen levels.
Article
Genetics & Heredity
Hiroki Hosoi, Akiko Niibori-Nambu, Giselle Sek Suan Nah, Avinash Govind Bahirvani, Michelle Meng Huang Mok, Takaomi Sanda, Alan Prem Kumar, Daniel G. Tenen, Yoshiaki Ito, Takashi Sonoki, Motomi Osato
Summary: The study demonstrates the crucial role of super-enhancers for the expression of RUNX3 and MYC in EBV-positive malignant B cells. The deletion of super-enhancers resulted in the downregulation of both genes, leading to suppressed cell proliferation and colony formation. These findings suggest that seR3s could be a potential therapeutic target for EBV-related tumors.
Article
Microbiology
Rachel Hood Edwards, Nancy Raab-Traub
Summary: This study evaluated the impact of EBV and BART lncRNAs on cellular expression, showing that they induce changes in cellular miRs and lncRNAs. In vivo expression changes reflect increased cellular miRs in all tumors, while the BART lncRNA may inhibit the function of induced cellular miRs. The study provides insights into the total effects of EBV and BART lncRNA on cellular RNA expression.
Article
Microbiology
Quincy Rosemarie, Elijah Kirschstein, Bill Sugden
Summary: We have discovered how Epstein-Barr virus (EBV) induces the reorganization of cellular chromatin, with viral DNA replication occurring in the chromatin-free regions. Five families of DNA viruses induce similar reorganization, and they infect a variety of hosts. The viral genes and processes required for EBV's chromatin reorganization have been identified, and a two-step model for the process has been proposed. The importance of chromatin reorganization in viral life cycles is emphasized. Overall, a 9 out of 10 score is given for the importance of this research.
Review
Cell Biology
Chin-King Looi, Lian-Chee Foong, Felicia Fei-Lei Chung, Alan Soo-Beng Khoo, Ee-Mun Loo, Chee-Onn Leong, Chun-Wai Mai
Summary: This review provides updated understanding of the roles of epigenetic factors in regulating EBV latent gene expression and promoting NPC progression. The crosstalk between epigenetic mechanisms and immune evasion in NPC is explored, along with the potential roles of DNMT and HDAC inhibitors in reversing immune suppression and augmenting antitumour immunity. Furthermore, the advantages of combining epigenetic therapy and immune checkpoint inhibitor to reverse immune resistance and improve clinical outcomes are highlighted.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Gastroenterology & Hepatology
Hui Song, Yan Zhang, Juanjuan Liu, Wen Liu, Bing Luo
Summary: The study revealed a new mechanism of EBV in regulating the expression of DNMT3a in EBV-associated gastric carcinoma. Targeting the EBNA1/E2F1/DNMT3a axis could be a potential therapeutic strategy for EBVaGC with high DNMT3a expression.
DIGESTIVE AND LIVER DISEASE
(2022)
Review
Oncology
Ramon Yarza, Mateo Bover, Maria Teresa Agullo-Ortuno, Lara Carmen Iglesias-Docampo
Summary: Nasopharyngeal carcinoma (NPC) is a molecularly paradigmatic tumor with complex environmental and host dependent factors, where Epstein Barr Virus (EBV) plays a key role in malignant transformation. The dysregulation of proteasome signaling is central in NPC pathogenesis and could be a potential therapeutic target. Studies have shown the efficacy of immunotherapy in NPC, with novel strategies aiming to reverse immune resistance and favor tumor recognition.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Wenzhe Li, Atsushi Okabe, Genki Usui, Masaki Fukuyo, Keisuke Matsusaka, Bahityar Rahmutulla, Yasunobu Mano, Takayuki Hoshii, Sayaka Funata, Nobuhiro Hiura, Masashi Fukayama, Patrick Tan, Tetsuo Ushiku, Atsushi Kaneda
Summary: The study showed that EBV infection contributes to gastric tumorigenesis by activating enhancers, with EHF playing a critical role in the process. Additionally, genes associated with the WNT signaling pathway in cancer were significantly enriched in EBV-positive GC.
Article
Cell Biology
Kenji Ito, Kohei Nagata, Sho Ohta, Yutaka Matsuda, Tomoyo Ukai, Ichiro Yasuda, Akira Ota, Ryota Kobayashi, Mio Kabata, Nao Sankoda, Tatsuya Maeda, Knut Woltjen, Liying Yang, Reo Maruyama, Ryohei Katayama, Takuya Yamamoto, Yasuhiro Yamada
Summary: Resistance to transcription factor-mediated reprogramming into pluripotent stem cells is a distinctive feature of cancer cells, but studying the profiles of reprogramming factor binding and transcriptional response can reveal underlying mechanisms and potential therapeutic targets. In cancer cells, oncogenes like EWS/ATF1 can misdirect reprogramming factors to specific enhancers, inhibiting the transcriptional response towards pluripotency. Pharmacological inhibition of corresponding oncogenic signals can sensitize cancer cells to reprogramming cues, while targeting downstream signaling pathways like mTOR can attenuate cancer cell propagation. This highlights the potential for early transcriptional responses to guide the identification of effective therapeutics targets in cancer cells.
Review
Biochemistry & Molecular Biology
Ying Hua Su, Li Ping Tang, Xiang Yu Zhao, Xian Sheng Zhang
Summary: Plant cells have a strong capacity for reproduction, as a single plant cell can give rise to a whole plant via somatic embryogenesis without fertilization. Reprogramming somatic cells into totipotent cells is a critical step in somatic embryogenesis, inducible by stimuli such as plant hormones, transcriptional regulators and stress. Key molecular regulators and associated networks that control cell fate transition from somatic to totipotent cells are highlighted, with several outstanding questions proposed for further understanding of plant cell totipotency mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiajun Xie, Zifeng Wang, Wenjun Fan, Youping Liu, Fang Liu, Xiangbo Wan, Meiling Liu, Xuan Wang, Deshun Zeng, Yan Wang, Bin He, Min Yan, Zijian Zhang, Mengjuan Zhang, Zhijie Hou, Chunli Wang, Zhijie Kang, Wenfeng Fang, Li Zhang, Eric W-F Lam, Xiang Guo, Jinsong Yan, Yixin Zeng, Mingyuan Chen, Quentin Liu
Summary: The study reveals that EBV latent protein LMP1 induces cellular dedifferentiation and stem-like status by inhibiting histone acetylation of the CEBPA gene. HDAC inhibition can restore CEBPA expression and reverse this cellular status. This suggests a promising concept of differentiation therapy in solid tumors using HDAC inhibitors to target cellular plasticity.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Virology
Mingqian Xu, Liang Zhang, Jinfu Feng, Shuaibing Yang, Yixuan Wang, Yuyi Wang, Meiyang Chen, Li Zhou, Junjie Zhang, Qingsong Qin
Summary: EBV-associated gastric cancer is a subtype of gastric cancer characterized by the presence of EBV genome and limited viral gene expression in malignant epithelial cells. Two EBV-positive gastric cancer cell lines have been established to study the role of EBV in different contexts of gastric carcinogenesis. These cell lines can serve as models to investigate the role of EBV in gastric cancer and identify new therapeutics against EBVaGC.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Omkar Indari, Annu Rani, Budhadev Baral, Suleyman Ergun, Kiran Bala, Srikanth Karnati, Hem Chandra Jha
Summary: Viruses exploit peroxisomal compartment for successful infection. This study investigates the modulation of peroxisomal proteins in EBV transformed cell lines and during acute EBV infection. The results reveal distinct regulation of peroxisomal proteins in EBV infected cells and highlight the importance of investigating the manipulation of the peroxisomal compartment in EBV pathologies.
MICROBIAL PATHOGENESIS
(2023)
Article
Multidisciplinary Sciences
Xiao Zhang, Junping Hong, Ling Zhong, Qian Wu, Shanshan Zhang, Qianying Zhu, Haiwen Chen, Dongmei Wei, Rui Li, Wanlin Zhang, Xinyu Zhang, Guosong Wang, Xiang Zhou, Junyu Chen, Yinfeng Kang, Zhenghui Zha, Xiaobing Duan, Yang Huang, Cong Sun, Xiangwei Kong, Yan Zhou, Yanhong Chen, Xiaoping Ye, Qisheng Feng, Shaowei Li, Tong Xiang, Song Gao, Mu-Sheng Zeng, Qingbing Zheng, Yixin Chen, Yi-Xin Zeng, Ningshao Xia, Miao Xu
Summary: This study identified two neutralizing antibodies that effectively neutralize EBV infection and provide protection against EBV-induced lymphoproliferative disorders in humanized mice. The antibodies inhibit membrane fusion through interference with gB-cell interaction and activation, offering potential targets for antiviral therapies and vaccines.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Xubing Long, Ziwei Yang, Yang Li, Qinqin Sun, Xiaojuan Li, Ersheng Kuang
Summary: The study reveals that BRLF1 regulates cellular and viral gene expression and transcription during EBV primary infection, impacting pathways such as DNA replication and metabolism. BRLF1 binds to transcription factors and spliceosome components, influencing RNA polymerase II-dependent transcription and pre-mRNA splicing.
Article
Immunology
Anna Sledzinska, Maria Vila de Mucha, Katharina Bergerhoff, Alastair Hotblack, Dafne Franz Demane, Ehsan Ghorani, Ayse U. Akarca, Maria A. Marzolini, Isabelle Solomon, Frederick Arce Vargas, Martin Pule, Masahiro Ono, Benedict Seddon, George Kassiotis, Charlotte E. Ariyan, Thomas Kom, Teresa Marafioti, Graham M. Lord, Hans Stauss, Richard G. Jenner, Karl S. Peggs, Sergio A. Quezada
Review
Biochemistry & Molecular Biology
Claire Wilson, Aditi Kanhere
Summary: The 8q24.21 locus contains a high number of lncRNAs and is associated with an increased risk of cancer, showcasing the clinical relevance of lncRNAs in different cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Angelos Papadopoulos, Varvara Chalmantzi, Olga Mikhaylichenko, Marko Hyvonen, Dimitris Stellas, Aditi Kanhere, John Heath, Debbie L. Cunningham, Theodore Fotsis, Carol Murphy
Summary: This study investigates the effects of Activin A and BMP4 on human embryonic stem cells, revealing their crucial regulatory roles in determining cell fate decisions. The findings highlight the importance of WNT signaling in maintaining pluripotency and promoting differentiation in hESCs.
STEM CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Rhian Jones, Susanne Wijesinghe, Claire Wilson, John Halsall, Triantafillos Liloglou, Aditi Kanhere
Summary: The nuclear lincRNA CCDC26 plays a crucial role in regulating DNMT1 activity and controlling DNA methylation levels. Its absence leads to mis-localization of DNMT1 to the cytoplasm, causing significant hypomethylation of genomic DNA, double-stranded DNA breaks, and increased cell death. This study reveals a previously unrecognized mechanism of lincRNA-mediated subcellular localization of DNMT1 and regulation of DNA methylation.
Article
Biochemistry & Molecular Biology
Sanjana Pillay, Hazuki Takahashi, Piero Carninci, Aditi Kanhere
Summary: During early vertebrate development, zebrafish NATs can be divided into two major classes based on their coexpression patterns with overlapping protein-coding genes. Group 1 NATs show characteristics similar to maternally deposited RNAs with levels decreasing as development progresses and negative correlation with overlapping sense-strand protein-coding genes, while Group 2 NATs are coexpressed with overlapping protein-coding genes and enriched in housekeeping functions.
Article
Gastroenterology & Hepatology
Rimma Goldberg, Jennie N. Clough, Luke B. Roberts, Jenifer Sanchez, Shahram Kordasti, Nedyalko Petrov, Arnulf Hertweck, Anna Lorenc, Ian Jackson, Scott Tasker, Anna Appios, Omer Omer, Miles Parkes, Natalie Prescott, Richard G. Jenner, Peter M. Irving, Graham M. Lord
Summary: The study reveals that IBD patients carrying the rs61839660 SNP show an enhanced T-eff immune phenotype with increased pro-inflammatory cytokine expression in response to IL-2 stimulation, while individuals with the TT genotype may exhibit a more active gut homing phenotype and reduced T cell clonal capacity.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Biochemistry & Molecular Biology
Lenka Skalska, Victoria Begley, Manuel Beltran, Saulius Lukauskas, Garima Khandelwal, Peter Faull, Amandeep Bhamra, Manuel Tavares, Rachel Wellman, Andrey Tvardovskiy, Benjamin M. Foster, Igor Ruiz de los Mozos, Javier Herrero, Silvia Surinova, Ambrosius P. Snijders, Till Bartke, Richard G. Jenner
Summary: Nascent RNA primarily antagonizes the interaction of chromatin modifiers and transcriptional regulators with chromatin, linking transcriptional output with chromatin composition by inhibiting their binding and recruitment.
Article
Biology
Stephen Henderson, Venu Pullabhatla, Arnulf Hertweck, Emanuele de Rinaldis, Javier Herrero, Graham M. Lord, Richard G. Jenner
Summary: The majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding is associated with differences in transcription factor-binding motifs and species-specific expression of associated genes.
LIFE SCIENCE ALLIANCE
(2021)
Article
Immunology
Jonathan W. Lo, Maria Vila de Mucha, Stephen Henderson, Luke B. Roberts, Laura E. Constable, Natividad Garrido-Mesa, Arnulf Hertweck, Emilie Stolarczyk, Emma L. Houlder, Ian Jackson, Andrew S. MacDonald, Nick Powell, Joana F. Neves, Jane K. Howard, Richard G. Jenner, Graham M. Lord
Summary: This study demonstrates the expression of T-bet in a subset of CD4(+) T cells with naive cell characteristics, and shows that these T-bet-expressing cells have distinct phenotypic and functional properties from previously described cell subsets. Naive-like T-bet-experienced cells are polarized to the T(H)1 lineage and resist repolarization to other lineages.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Oncology
Alessandro Agnarelli, Simon Mitchell, Gillian Caalim, C. David Wood, Leanne Milton-Harris, Timothy Chevassut, Michelle J. West, Erika J. Mancini
Summary: The B-cell progenitor fate determinant IRF4 plays a crucial role in the pathogenesis and progression of multiple myeloma (MM). This study evaluates the use of bromodomain inhibitors to target the IRF4-MYC axis and finds that bromodomain inhibition primarily functions through MYC rather than IRF4. These findings suggest that novel therapeutic strategies for MM should focus on directly inhibiting or degrading IRF4.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arnulf Hertweck, Maria Vila de Mucha, Paul R. Barber, Robert Dagil, Hayley Porter, Andres Ramos, Graham M. Lord, Richard G. Jenner
Summary: This study reveals that lineage-determining transcription factors (LD-TFs) can drive specific cell fate choices by redistributing another transcription factor, even in the presence of other factors driving alternative differentiation pathways.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Manuel Tavares, Garima Khandelwal, Joanne Muter, Keijo Viiri, Manuel Beltran, Jan J. Brosens, Richard G. Jenner
Summary: The fusion protein JAZF1-SUZ12 dysregulates PRC2 composition, gene expression, and cell differentiation, and may play an important role in oncogenesis.
Article
Food Science & Technology
Wided Souissi, Tweedie Alistair, Barbara Domanska, Eva Fortea, Michelle J. West, Jean-Louis Schwartz, Neil Crickmore
Summary: This study identifies Cry41Aa as a toxin that exhibits cytotoxic activity against human liver cancer cells and leukemia cells. Resistance to Cry41Aa can be developed in cells through repeated exposure to increasing doses of the toxin. However, resistant cells do not show characteristic features of pore-forming toxins and the specific resistance mechanism remains unclear.
Article
Gastroenterology & Hepatology
Omer S. Omer, Arnulf Hertweck, Luke B. Roberts, Jonathan W. Lo, Jennie N. Clough, Ian Jackson, Eirini D. Pantazi, Peter M. Irving, Tom T. MacDonald, Polychronis Pavlidis, Richard G. Jenner, Graham M. Lord
Summary: Targeting the transactivation function of T-bet using CDK9 inhibitors can improve immune-mediated colitis in IBD patients and selectively suppress genes responsible for pro-inflammatory signaling, especially those regulated by T-bet. CDK9 inhibition may also be a potential therapeutic target for anti-TNF-resistant IBD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarika Khasnis, Hildegonda Veenstra, Michael J. McClellan, Opeoluwa Ojeniyi, C. David Wood, Michelle J. West
Summary: The Epstein-Barr virus (EBV), associated with cancer, manipulates the B cell receptor signaling pathway to control cell growth and survival. EBV transcription factors EBNA2, 3A, 3B, and 3C were found to bind to genomic sites around B cell receptor pathway genes, regulating their expression and affecting B cell receptor signaling. EBNA2 and EBNA3 predominantly repress the expression of B cell receptor pathway genes and target common genes. EBNA2 and at least one EBNA3 protein repress the central components of the B cell receptor pathway and downstream genes. This study reveals a mechanism through which EBV controls the growth and survival of infected B cells and maintains viral latency.
BIOCHEMICAL JOURNAL
(2022)