Article
Multidisciplinary Sciences
Maxine S. Y. Lam, Jose Antonio Reales-Calderon, Jin Rong Ow, Joey J. Y. Aw, Damien Tan, Ragavi Vijayakumar, Erica Ceccarello, Tommaso Tabaglio, Yan Ting Lim, Wang Loo Chien, Fritz Lai, Anthony Tan Tanoto, Qingfeng Chen, Radoslaw M. Sobota, Giulia Adriani, Antonio Bertoletti, Ernesto Guccione, Andrea Pavesi
Summary: In this study, the authors used an inhibitor targeting the epigenetic regulator G9a/GLP to enhance the antitumor activity of engineered T cells. The results in vitro and in vivo demonstrated improved T cell cytotoxicity and tumor reduction.
NATURE COMMUNICATIONS
(2023)
Review
Plant Sciences
Huihui Fang, Yuke Shao, Gang Wu
Summary: This review discusses the reprogramming of histone H3 methylation during plant sexual reproduction, highlighting its importance in cell specification and establishment of pluripotency. Despite advancements in understanding this process, challenges remain in this area and future breakthroughs in cell-specific epigenomic profiling are expected to provide a solution.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Endocrinology & Metabolism
Ye-Chi Cao, Su-Kang Shan, Bei Guo, Chang-Chun Li, Fu-Xing-Zi Li, Ming-Hui Zheng, Qiu-Shuang Xu, Yi Wang, Li-Min Lei, Ke-Xin Tang, Wen-Lu Ou-Yang, Jia-Yue Duan, Yun-Yun Wu, Muhammad Hasnain Ehsan Ullah, Zhi-Ang Zhou, Feng Xu, Xiao Lin, Feng Wu, Xiao-Bo Liao, Ling-Qing Yuan
Summary: Histone methylation modification may play a key role in the development of vascular calcification, which involves various complex pathophysiological processes. Comprehensive research on the role and mechanism of lysine methylation modification in VC is crucial for identifying new therapeutic targets and developing new drugs.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Analytical
Laure Bar, Christophe Nguyen, Mathieu Galibert, Francisco Santos-Schneider, Gudrun Aldrian, Jerome Dejeu, Remy Lartia, Liliane Coche-Guerente, Franck Molina, Didier Boturyn
Summary: Antibodies are not only important for clinical diagnostics and biopharmaceutical analysis, but also as drugs for treating various diseases. The identification of antibody-epitope binding sites, particularly for designing monoclonal antibody mimics like rituximab, is crucial for medical and bioanalytical applications. Rituximab, a monoclonal antibody used to treat cancers and autoimmune disorders, binds to targeted cells via the recognition of the CD20 epitope, with its binding area located on the surface of rituximab.
ANALYTICAL CHEMISTRY
(2021)
Article
Microbiology
Susana Munguia-Robledo, Esther Orozco, Guillermina Garcia-Rivera, Jeni Bolanos, Jesus Valdes, Elisa Azuara-Liceaga, Mario Alberto Rodriguez
Summary: Lysine methylation, catalyzed by PKMTs, is involved in epigenetics and signaling pathways and may participate in virulence of protozoa parasites. This study found that EhPKMT2 is involved in cellular events such as phagocytosis and heat shock and has effects on cell growth, migration, and cytopathic effect, suggesting it as a potential therapeutic target for amebiasis.
Review
Biochemistry & Molecular Biology
Ying Li, Lei Ding, Shuang Ren, Wen Zhang, Guo-Wu Rao
Summary: Protein lysine methylation is an important protein post-translational modification involved in epigenetic regulation. Aberrant activity of protein lysine methyltransferase (PKMTs) has been found in various cancers and diseases, and PKMT inhibitors have been discovered and progressed to clinical trials. This field has developed rapidly and attracted significant interest.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Biology
Martin Rougee, Leandro Quadrana, Jerome Zervudacki, Valentin Hure, Vincent Colot, Lionel Navarro, Angelique Deleris
Summary: DNA methylation and H3K27me3 are two specialized systems for epigenetic silencing in plants and mammals, but the acquisition of H3K27me3 at TE sequences can depend on CURLY LEAF and does not necessarily lead to TE reactivation or increased transposition.
LIFE SCIENCE ALLIANCE
(2021)
Article
Chemistry, Physical
Wan-Sheng Ren, Adua Rahman, Kai-Bin Jiang, Hao Deng, Yuan-Yuan Zhao, Wei-Jie Zhang, Kedian Liu, Ping Qian, Hong Guo
Summary: PRMT7 is the only known member of type III PRMT that produces monomethyl arginine (MMA) product. Simulations and analysis are performed to understand the mechanism of E181D and E181D/Q329A mutants in generating ADMA and SDMA products, identifying important factors contributing to the change in activity and product specificity due to mutations.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Review
Endocrinology & Metabolism
Lucie Malbeteau, Ha Thuy Pham, Louisane Eve, Michael R. Stallcup, Coralie Poulard, Muriel Le Romancer
Summary: Steroid receptors (SRs) are important members of the nuclear hormonal receptor family, regulating various physiological functions essential for human health. Dysregulation of SRs may contribute to a wide range of pathologies, highlighting the significance of understanding their regulatory mechanisms.
Article
Multidisciplinary Sciences
Bo Yu, Jun Su, Qiqi Shi, Qing Liu, Jun Ma, Guoqing Ru, Lei Zhang, Jian Zhang, Xichun Hu, Jianming Tang
Summary: This study identifies a new regulatory mechanism for SNIP1, in which it is methylated by KMT5A to initiate oncogenic functions. The study also reveals how SNIP1 methylation promotes breast cancer cell growth, invasion, and lung metastasis, and drives tumorigenesis and metastasis by activating the YAP pathway.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Yanguang Hou, Yan Yuan, Yanze Li, Lei Wang, Juncheng Hu, Xiuheng Liu
Summary: Renal cell carcinoma, accounting for 2-3% of all cancers, is challenging to diagnose early. Recent genome-wide studies have found that histone methylation is commonly dysregulated in renal cell cancer. Mutations or dysregulation of histone methylation, methyltransferases, and demethylases are associated with gene expression and tumor progression in renal cell cancer.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Cell Biology
Ke Wang, Wan Huang, Ruo Chen, Peng Lin, Tao Zhang, Yun-Feng Ni, Hao Li, Jiao Wu, Xiu-Xuan Sun, Jie-Jie Geng, Yu-Meng Zhu, Gang Nan, Wei Zhang, Xi Chen, Ping Zhu, Huijie Bian, Zhi-Nan Chen
Summary: CD147, methylated to CD147-K234me2 by KMT5A, plays a critical role in cancer metabolism by enhancing glycolysis and lactate export in NSCLC cells. High CD147-K234me2 expression is significantly related to cancer progression and overall survival in NSCLC patients, especially those in early stages, suggesting it as a promising therapeutic target.
Article
Multidisciplinary Sciences
Che-Fan Huang, Cara J. Gottardi, Milan Mrksich
Summary: Phosphorylation plays a crucial role in cellular signaling, and dysregulation of phosphorylation can lead to diseases. However, while most studies focus on kinases, the role of phosphatases is often overlooked. This study demonstrates that basic amino acids adjacent to phosphotyrosines can restrict the activity of tyrosine phosphatases, providing insights into the mechanisms underlying disease-associated mutations and potential treatment strategies.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Carlos Moreno-Yruela, Michael Baek, Adela-Eugenie Vrsanova, Clemens Schulte, Hans M. Maric, Christian A. Olsen
Summary: Researchers successfully captured HDAC using hydroxamic acid-modified microarray technology, providing insights into their substrate specificity and facilitating inhibitor development.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Sha Liu, Xiang Li, Xin Li, Xiang David Li
Summary: Inhibitors targeting epigenetic readers serve as useful probes to study the functional roles of these targets in epigenetic regulation, and can also be used as drugs for treating diseases associated with dysregulated targets. However, many epigenetic readers are difficult to target with small molecules due to their recognition of modified histone peptides, which commonly involves flat and extended protein surfaces. Peptide-based inhibitors have larger sizes and structural complexity, allowing for tight and specific binding to the target proteins. This review discusses the recent advances in peptide-based inhibitors for lysine acetylation and methylation readers.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julian Broche, Goran Kungulovski, Pavel Bashtrykov, Philipp Rathert, Albert Jeltsch
Summary: This study revealed that DNA methylation introduced in CGIs can significantly decrease gene expression, and is associated with a global decrease in H3K4me3 and H3K27ac, while being stable at some CGIs. The results highlight the importance of genome-wide molecular processes that protect CGIs against DNA methylation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Erna Davydova, Tadahiro Shimazu, Maren Kirstin Schuhmacher, Magnus E. Jakobsson, Hanneke L. D. M. Willemen, Tongri Liu, Anders Moen, Angela Y. Y. Ho, Jedrzej Malecki, Lisa Schroer, Rita Pinto, Takehiro Suzuki, Ida A. Gronsberg, Yoshihiro Sohtome, Mai Akakabe, Sara Weirich, Masaki Kikuchi, Jesper V. Olsen, Naoshi Dohmae, Takashi Umehara, Mikiko Sodeoka, Valentina Siino, Michael A. McDonough, Niels Eijkelkamp, Christopher J. Schofield, Albert Jeltsch, Yoichi Shinkai, Pal O. Falnes
Summary: Post-translational methylation, specifically protein histidine methylation, is crucial for optimizing protein function. METTL9 is identified as a broad-specificity methyltransferase responsible for the majority of 1-methylhistidine modifications in mouse and human proteomes. The methylation catalyzed by METTL9 enhances respiration via Complex I, and reduces the zinc binding affinity of HxH-containing peptides.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Viviane Klingel, Jakob Kirch, Timo Ullrich, Sara Weirich, Albert Jeltsch, Nicole E. Radde
Summary: The study developed a novel mathematical model to describe the switching dynamics of methylation-based epigenetic memory systems, which revealed a high sensitivity to variations in temperature. A moderate decrease in temperature led to a highly heterogeneous response to input signals and bistability on a single-cell level, confirming the model's predictions.
Article
Biology
Sabrina Adam, Julia Bracker, Viviane Klingel, Bernd Osteresch, Nicole E. Radde, Jens Brockmeyer, Pavel Bashtrykov, Albert Jeltsch
Summary: This study reveals that the catalytic activities of TET1 and TET2 are influenced by the flanking sequences of DNA substrates, and this influence is related to 5mC and 5hmC. Furthermore, enhanced flanking sequence preferences and profound effects on the specificity of TET2 are observed at non-CpG sites. The flanking sequence preferences of TET are reflected in genome-wide and local patterns of 5hmC and DNA demethylation.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Mack, Max Emperle, Philipp Schnee, Sabrina Adam, Juergen Pleiss, Pavel Bashtrykov, Albert Jeltsch
Summary: Somatic R882H DNMT3A mutations are common in AML, but their pathogenic mechanism is unclear. R882H mutations affect the sequence preferences of DNMT3A and have a dominant effect on its catalytic properties in samples containing WT and R882H subunits.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
Alexander Broehm, Tabea Schoch, Michael Dukatz, Nora Graf, Franziska Dorscht, Evelin Mantai, Sabrina Adam, Pavel Bashtrykov, Albert Jeltsch
Summary: DNMT3A efficiently methylates recombinant mononucleosome linker DNA, and H3K36me3 stimulates linker DNA methylation independent of its interaction with the PWWP domain.
COMMUNICATIONS BIOLOGY
(2022)
Editorial Material
Biology
Arunkumar Dhayalan, Albert Jeltsch
Article
Biochemistry & Molecular Biology
Alexander Broehm, Tabea Schoch, David Gruenberger, Mina S. Khella, Maren Kirstin Schuhmacher, Sara Weirich, Albert Jeltsch
Summary: The H3.3 G34W mutation is commonly found in giant cell tumor of bone (GCTB) patients and is associated with reduced SETD2 activity and global reduction in DNA methylation. Our study reveals that the G34W mutation enhances the activity of NSD1 methyltransferase, but has mild effects on NSD2. We discuss the potential downstream effects of the G34W-induced hyperactivity of NSD1 on DNA methylation, histone modifications, and splicing.
Article
Chemistry, Multidisciplinary
Philipp Schnee, Michel Choudalakis, Sara Weirich, Mina S. Khella, Henrique Carvalho, Juergen Pleiss, Albert Jeltsch
Summary: This study investigates the mechanisms responsible for the increased activity of SETD2 towards ssK36 peptide. Molecular dynamics simulations and biochemical experiments reveal that ssK36 adopts a hairpin conformation in solution and unfolds during the association process with SETD2. Introducing a stable hairpin conformation increases the methylation of H3K36 peptide by SETD2.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Stefan Kunert, Max Emperle, Sabrina Adam, Julia Bracker, Jens Bracker, Arumugam Rajavelu, Albert Jeltsch
Summary: The DNMT3A DNA methyltransferase is frequently mutated in cancers, especially in AML. The R736H mutation in the FF-interface of the enzyme leads to a moderate reduction in catalytic activity but no changes in CpG specificity or sub-nuclear localization. DNMT3L strongly stimulates the activity of R736H, and mixed interfaces involving R736H also enhance the activity.
Article
Biochemistry & Molecular Biology
Dimitri Graf, Laura Laistner, Viviane Klingel, Nicole E. Radde, Sara Weirich, Albert Jeltsch
Summary: A DNA methylation-based epigenetic memory system was developed to detect environmental signals and trigger phenotypic switches in bacteria. The system's reversible reset was achieved by adding ZnSO4, and the long-term stability of the ON-state was studied, showing a gradual loss of signal over time.
Article
Biology
Julian Broche, Anja R. R. Koehler, Fiona Kuehnel, Bernd Osteresch, Thyagarajan T. T. Chandrasekaran, Sabrina Adam, Jens Brockmeyer, Albert Jeltsch
Summary: Although cytosine-C5 methylation of DNA is essential in higher eukaryotes, the presence and importance of 6-methyladenine (m6dA) in human cells are controversial. We introduced m6dA in human cells and observed reductions in cell viability, particularly after global GANTC methylation. Genes directly regulated by m6dA in a GANTC context showed changes in H3K27me3 and JUN family transcription factor binding, indicating an inhibitory effect on the PRC2 complex and reduced recruitment of JUN transcription factors. Our study demonstrates the physiological effects of m6dA introduction in human DNA and identifies target genes and molecular pathways that affect gene expression and cell phenotypes.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sabrina Adam, Viviane Klingel, Nicole E. Radde, Pavel Bashtrykov, Albert Jeltsch
Summary: The specificity of DNMT1 for hemimethylated DNA is strongly influenced by the flanking sequence, with an average specificity of 80-fold. This preference is enhanced on long hemimethylated DNA substrates. The presence of a single methyl group in the DNA changes the conformation of the DNMT1-DNA complex, leading to an active conformation by steric repulsion. Passive DNA demethylation by 5hmC generation is not efficient in many flanking contexts.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Nivethika Rajaram, Alexandra G. Kouroukli, Susanne Bens, Pavel Bashtrykov, Albert Jeltsch
Summary: Specific allele-specific targeted DNA methylation was achieved at multiple gene loci using epigenome editing, which can be potentially applied in the treatment of diseases caused by dominant mutations with minimal side effects.
EPIGENETICS & CHROMATIN
(2023)
Editorial Material
Multidisciplinary Sciences
Sara Weirich, Albert Jeltsch
Summary: Protein lysine methylation is important but lacks suitable mimetics for experimental characterization. This limits biochemical and cellular studies. We summarize the challenges and propose alternative approaches.
NATURE COMMUNICATIONS
(2023)
