Article
Chemistry, Multidisciplinary
Yan Gao, Xinlei Sheng, Doudou Tan, SunJoo Kim, Soyoung Choi, Sanjita Paudel, Taeho Lee, Cong Yan, Minjia Tan, Kyu Min Kim, Sam Seok Cho, Sung Hwan Ki, He Huang, Yingming Zhao, Sangkyu Lee
Summary: This study identifies acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized histone post-translational modification. It also finds that HBO1 can function as both an acetyltransferase and an acetoacetyltransferase. Additionally, 33 Kacac sites are identified on mammalian histones, providing insight into the distribution of this modification across species and organs.
Article
Biochemical Research Methods
Sony Shrestha, Amuza Byaruhanga Lucky, Awtum Marie Brashear, Xiaolian Li, Liwang Cui, Jun Miao
Summary: This study profiled the histone post-translational modifications (PTMs) in the development of Plasmodium falciparum gametocytes, revealing novel PTM sites and distinct patterns from asexual stages. The results suggest that these PTMs play critical roles in gametocyte development and provide insights into the epigenetic regulation in the life cycle of the malaria parasite.
JOURNAL OF PROTEOME RESEARCH
(2022)
Review
Medicine, Research & Experimental
Dongze Li, Li Zhang, Yanqiu He, Tingting Zhou, Xi Cheng, Wei Huang, Yong Xu
Summary: Diabetes is a prevalent global epidemic disease that is influenced by genetic, environmental, and socioeconomic factors. Histone post-translational modifications, specifically methylation and acetylation, play significant roles in the pathophysiological changes associated with diabetes. Recent advancements in mass spectrometry have identified novel histone acylation modifications, which are yet to be thoroughly investigated for their connection to diabetes.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemical Research Methods
Yuan Lin, Archana M. Agarwal, Alan G. Marshall, Lissa C. Anderson
Summary: Hemoglobinopathies, a prevalent genetic disorder, can be effectively identified and characterized through mass spectrometry. R scripts developed by the authors aid in rapid and reliable identification of hemoglobin variants, while chimeric ion loading technique enables simultaneous detection in a high-resolution mass spectrometer.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Analytical
Ning Xia, Ting Sun, Lin Liu, Linxu Tian, Zhifang Sun
Summary: The study introduces a novel sensing platform utilizing avidin-modified interface and biotin-labeled substrates as probes for heterogeneous analysis, combining the advantages of homogeneous and heterogeneous assays while overcoming their limitations.
Article
Cell Biology
Angelique Sanchez Dafun, Dusan Zivkovic, Stephen Adonai Leon-Icaza, Sophie Moeller, Carine Froment, Delphine Bonnet, Adriana Almeida de Jesus, Laurent Alric, Muriel Quaranta-Nicaise, Audrey Ferrand, Celine Cougoule, Etienne Meunier, Odile Burlet-Schiltz, Frederic Ebstein, Raphaela Goldbach-Mansky, Elke Krueger, Marie-Pierre Bousquet, Julien Marcoux
Summary: The mammalian 20S catalytic core of the proteasome is composed of 14 different subunits and exists as different subtypes depending on cell type. Proteasome activity is altered by post-translational modifications and genetic variants. A new miniaturized workflow combining top-down and bottom-up mass spectrometry is presented for analyzing proteasome assembly status and full proteoform footprint.
Review
Pharmacology & Pharmacy
Elena Kunadis, Eleftheria Lakiotaki, Penelope Korkolopoulou, Christina Piperi
Summary: Glioblastoma is the most common primary brain tumor in adults, characterized by variable histopathology, aggressiveness, and poor clinical outcomes. Epigenetic modifications play a crucial role in GBM research, providing a potential for tumor classification and prognosis, as well as for drug targeting. Recent advances in glioma epigenetic research focus on histone modifications and the use of epigenetic therapy as a valid treatment option for glioblastoma.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Plant Sciences
Rocio Nunez-Vazquez, Benedicte Desvoyes, Crisanto Gutierrez
Summary: Plants have developed various mechanisms to adapt to abiotic stresses, which involve transcriptional regulation and chromatin modifications. Understanding and manipulating these regulatory networks are crucial for enhancing crop resilience and performance against stress.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Microbiology
Samantha N. Cobos, Chaim Janani, Gabriel Cruz, Navin Rana, Elizaveta Son, Rania Frederic, Jailene Paredes Casado, Maliha Khan, Seth A. Bennett, Mariana P. Torrente
Summary: In this study, the researchers explore the link between prion states and histone modifications in yeast. They find that different prion states are associated with specific changes in histone post-translational modifications. These findings provide novel insights into the function of prions in yeast.
Article
Oncology
Roberta Noberini, Evelyn Oliva Savoia, Stefania Brandini, Francesco Greco, Francesca Marra, Giovanni Bertalot, Giancarlo Pruneri, Liam A. McDonnell, Tiziana Bonaldi
Summary: This study simplified the protein extraction process from low-amount clinical samples and developed a protocol that allows MS-based analysis of histone PTMs from laser microdissected tissue areas with as low as 1000 cells, which is approximately 500 times lower than what is required by available methods. This method opens the possibility for spatial epi-proteomics, facilitating the investigation of epigenetic features in tissue and tumor heterogeneity and aiding in the discovery of novel epigenetic biomarkers and mechanisms.
CLINICAL EPIGENETICS
(2021)
Review
Microbiology
Yiman Li, Zhihui Song, Ente Wang, Liming Dong, Jie Bai, Dong Wang, Jinyan Zhu, Chao Zhang
Summary: Invasive aspergillosis is a significant cause of death in patients with hematological malignancies and transplant recipients. Antifungal drug resistance has become a concern in managing infections, and understanding histone posttranslational modifications may provide insights for developing new antifungal drugs.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Cell Biology
Mingyue Zheng, Guoxiang Jin, Zhongjun Zhou
Summary: Lamins, ancient intermediate filament proteins, are functionally regulated by post-translational modifications, contributing to various biological functions. Deregulation of lamins is associated with abnormal nuclear morphology and chromatin disorganization, leading to diseases. Understanding these modifications provides new insights into the molecular mechanisms underlying diseases and potential therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Yingying Lin, Ting Qiu, Guifeng Wei, Yueyue Que, Wenxin Wang, Yichao Kong, Tian Xie, Xiabin Chen
Summary: Inflammation is a defensive reaction to external stimuli in the human body and is associated with various diseases. Histone modifications play a significant role in the regulation of inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Dimitrios Tsikas
Summary: Lysine residues in proteins undergo various chemical modifications, including carbonylation by glyoxal (GO) and methylglyoxal (MGO). Malondialdehyde (MDA) is another carbonyl species formed enzymatically and nonenzymatically. These carbonyl species can occur in free forms or be adducted to proteins, particularly lysine residues. MDA is commonly used as a biomarker of lipid peroxidation, with plasma and serum being the most frequently analyzed samples. However, preanalytical factors, such as artificial MDA formation in lipid-rich samples, can greatly affect MDA concentrations.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dan Wu, Tao Liu
Summary: Understanding post-translational modifications is crucial for manipulating physiological processes in eukaryotes. Genetic code expansion technology has been used to investigate the roles of these modifications, and can be combined with synthetic biology to create genetically modified organisms. This article discusses the applications, limitations, and future perspectives of genetic code expansion technology for studying post-translational modifications, as well as the implications for genetically modified organisms.
Review
Cell Biology
Siwanon Jirawatnotai, Stephen Dalton, Methichit Wattanapanitch
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Amar M. Singh, Liang Zhang, John Avery, Amelia Yin, Yuhong Du, Hui Wang, Zibo Li, Haian Fu, Hang Yin, Stephen Dalton
NATURE COMMUNICATIONS
(2020)
Article
Cell & Tissue Engineering
Liang Zhang, John Avery, Amelia Yin, Amar M. Singh, Timothy S. Cliff, Hang Yin, Stephen Dalton
Article
Multidisciplinary Sciences
Fabian Grubert, Rohith Srivas, Damek Spacek, Maya Kasowski, Mariana Ruiz-Velasco, Nasa Sinnott-Armstrong, Peyton Greenside, Anil Narasimha, Qing Liu, Benjamin Geller, Akshay Sanghi, Michael Kulik, Silin Sa, Marlene Rabinovitch, Anshul Kundaje, Stephen Dalton, Judith B. Zaugg, Michael Snyder
Review
Biochemistry & Molecular Biology
Nicolas L. Young, Ruhee Dere
Summary: Alterations in global epigenetic signatures on chromatin, specifically the overexpression of demethylase KDM4A, play a crucial role in tumor initiation and progression by modulating key cellular processes such as transcription and proliferation. This highlights the therapeutic potential of targeting KDM4A and other demethylases in cancer treatment.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Multidisciplinary Sciences
Lyra Chang, James Campbell, Idris O. Raji, Shiva K. R. Guduru, Prasanna Kandel, Michelle Nguyen, Steven Liu, Kevin Tran, Navneet K. Venugopal, Bethany C. Taylor, Matthew Holt, Nicolas L. Young, Errol L. G. Samuel, Prashi Jain, Conrad Santini, Banumathi Sankaran, Kevin R. MacKenzie, Damian W. Young
Summary: Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, a novel scaffold for targeting the isolated UHRF1 tandem Tudor domain (TTD) was identified using fragment-based ligand discovery. 2,4-lutidine was found to potentially evolve into more potent inhibitors for UHRF1 and provides a starting point for developing potent chemical probes against UHRF1.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Bethany C. Taylor, Nicolas L. Young
Summary: Histone post-translational modifications (PTMs) play a crucial role in regulating the genome by storing and transmitting complex signals about the genome state. Different PTM sites on the same histone molecule or nucleosome work in concert, supported by 'readers' structures, to transduce signals in specific cellular contexts.
BIOCHEMICAL JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Kyung-Won Park, Caleb A. Wood, Jun Li, Bethany C. Taylor, SaeWoong Oh, Nicolas L. Young, Joanna L. Jankowsky
Summary: Numerous aggregation inhibitors have been developed to block or reverse toxic amyloid formation in vivo, with recent studies focusing on short peptide inhibitors targeting different amyloidogenic regions. By creating a minigene to express full-length AO variants in the mouse brain, researchers have identified two variants that show promising therapeutic properties and used AAV delivery to express them in transgenic mice, leading to potential new strategies for Alzheimer's disease treatment, as well as a framework for developing tailored peptide inhibitors for other protein misfolding diseases.
Article
Genetics & Heredity
Bobby G. Ng, Paulina Sosicka, Francois Fenaille, Annie Harroche, Sandrine Vuillaumier-Barrot, Mindy Porterfield, Zhi-Jie Xia, Shannon Wagner, Michael J. Bamshad, Marie-Christine Vergnes-Boiteux, Sophie Cholet, Stephen Dalton, Anne Dell, Thierry Dupre, Mathieu Fiore, Stuart M. Haslam, Yohann Huguenin, Tadahiro Kumagai, Michael Kulik, Katherine McGoogan, Caroline Michot, Deborah A. Nickerson, Tiffany Pascreau, Delphine Borgel, Kimiyo Raymond, Deepti Warad, Heather Flanagan-Steet, Richard Steet, Michael Tiemeyer, Nathalie Seta, Arnaud Bruneel, Hudson H. Freeze
Summary: The study identified a recurrent mutation in SLC37A4 causing a dominantly inherited congenital disorder of glycosylation characterized by coagulopathy and liver dysfunction with abnormal serum N-glycans. Liver-specific abnormalities in glycosylation were replicated in a CRISPR base-edited hepatoma cell line carrying the mutation. The mutant protein showed relocation to a non-Golgi compartment and altered Golgi morphology and reduced intraluminal pH, potentially explaining the glycosylation alterations.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Multidisciplinary Sciences
Kyle N. Klein, Peiyao A. Zhao, Xiaowen Lyu, Takayo Sasaki, Daniel A. Bartlett, Amar M. Singh, Ipek Tasan, Meng Zhang, Lotte P. Watts, Shin-ichiro Hiraga, Toyoaki Natsume, Xuemeng Zhou, Timour Baslan, Danny Leung, Masato T. Kanemaki, Anne D. Donaldson, Huimin Zhao, Stephen Dalton, Victor G. Corces, David M. Gilbert
Summary: Loss of RIF1 disrupts the temporal order of DNA replication, leading to changes in chromatin modifications and genome architecture. Depletion of RIF1 causes increased heterogeneity between individual cells, resulting in replication-dependent disruption of histone modifications and alterations in genome architecture. These effects are magnified with successive cycles of altered replication timing.
Article
Biochemistry & Molecular Biology
Udom Lao-On, Timothy S. Cliff, Stephen Dalton, Sarawut Jitrapakdee
Summary: This study reveals that the ablation of the PC gene in brown adipocytes results in a 35% reduction in ATP-linked respiration, but does not affect thermogenesis, highlighting the crucial role of PC in supporting fuel oxidation rather than heat production in human brown adipocytes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Rebecca L. Murdaugh, Kevin A. Hoegenauer, Ayumi Kitano, Matthew Holt, Matthew C. Hill, Xiangguo Shi, Jonathan F. Tiessen, Richard Chapple, Tianyuan Hu, Yu-Jung Tseng, Angelique Lin, James F. Martin, Nicolas L. Young, Daisuke Nakada
Summary: Histone variant H3.3 is incorporated into genic elements independent of DNA replication by its chaperone HIRA, which is required for the self-renewal of adult hematopoietic stem cells (HSCs) and to restrain erythroid differentiation. Depletion of HSCs after Hira deletion is accompanied by increased expression of bivalent and erythroid genes, highlighting the role of HIRA-dependent H3.3 incorporation in defining repressive chromatin that represses erythroid differentiation of HSCs.
Article
Biochemical Research Methods
Xuan Wang, Zhongcheng Shi, Hsin-Yi Lu, Jean J. Kim, Wen Bu, Jose A. Villalobos, Dimuthu N. Perera, Sung Yun Jung, Tao Wang, Sandra L. Grimm, Bethany C. Taylor, Kimal Rajapakshe, Hyekyung Park, Julia Wulfkuhle, Nicolas L. Young, Yi Li, Cristian Coarfa, Dean P. Edwards, Shixia Huang
Summary: This study established an antibody-based reverse phase protein array platform for comprehensive profiling of post-translational modifications of histones and histone modifier proteins. The high throughput platform provides a valuable tool for analyzing epigenetics in biological and disease studies, and has potential applications in diagnostics and therapy development.
JOURNAL OF PROTEOMICS
(2022)
Review
Cell Biology
Faith M. Joseph, Nicolas L. Young
Summary: Post-translational modifications (PTMs) of histones play a key role in DNA-based processes and contribute to cell differentiation and gene function by adding an extra layer of regulation. Variations in histone sequences within each family of histones expand the chromatin repertoire and provide further mechanisms for regulation and signaling. However, much remains unknown about variant-specific PTMs and their role in regulating chromatin due to limited technologies and appropriate reagents.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Bethany C. Taylor, Nicolas L. Young
Summary: Histone proteins play a vital role in the regulation of the eukaryotic genome. This study demonstrates the first quantitative in vivo top-down analysis of histone H4 and compares the forebrains and hindbrains of differently aged mice. The results reveal differences in histone H4 post-translational modifications (PTMs) and proteoforms between brain regions and during adolescence. Lysine 20 methylation, however, remains constant with age and brain region.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
