Review
Developmental Biology
Alex Wei, Hao Wu
Summary: DNA methylation is a conserved epigenetic modification that is crucial for mammalian gene regulation, genome stability, and development. It can exhibit cell-type specificity and dynamic changes in gene regulatory elements during early embryonic development, stem cell differentiation, reprogramming, and tissue maturation. The interaction between DNA methylation and histone modifications plays a vital role in mammalian development and tissue maturation. Recent advances in technology have enabled high-resolution analysis of DNA methylome dynamics.
Article
Endocrinology & Metabolism
Beatriz Maria Veloso Pereira, Mariana Charleaux de Ponte, Ana Paula Malavolta Luz, Karina Thieme
Summary: This study aimed to show the expression profile of key DNA (de)methylation enzymes and their differences between sexes under obesity and diabetic condition. Female mice have a different profile of DNMTs expression, and metabolic condition negatively modulated the glomerular expression of TET1 and TET3 only in females. This study provides valuable knowledge on the epigenetic profile of DKD in males and females.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tarek K. Motawi, Shohda A. El-Maraghy, Dina Sabry, Omina M. Nady, Mahmoud A. Senousy
Summary: The study found that cromolyn chitosan nanoparticles (CSNPs) may have the potential as an epigenetic drug by inhibiting ERK1/2 phosphorylation and DNA methylation. In in vitro and in vivo experiments, cromolyn CSNPs showed significant anticancer effects and influenced the expression of DNMT1 and METTL3, impacting DNA and RNA methylation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Neurosciences
Seungjoon Lee, Hyojin Kang, Hwajin Jung, Eunjoon Kim, Eunee Lee
Summary: RNA-Seq analysis of Shank2 mutant mice revealed differential transcriptomic changes in brain regions at different gene dosages and ages, including upregulation of glutamate synapse-related genes and downregulation of ribosomal and mitochondrial genes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Microbiology
Xuechun Li, Wenjing Le, Xiangdi Lou, Caroline A. Genco, Peter A. Rice, Xiaohong Su
Summary: Neisseria gonorrhoeae isolates collected in Nanjing, China that showed decreased susceptibility or resistance to extended-spectrum cephalosporins (ESCs) were found to have varying susceptibility to ertapenem. The study also identified genetic determinants of ESC resistance and analyzed associations with ertapenem susceptibility. The findings suggest that ertapenem may be an effective therapy for ESC-resistant isolates with identifiable resistance determinants.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Xinuo Li, Dehong Shen, Zheying Zhu, Dayin Lyu, Chang He, Yuan Sun, Jinran Li, Qiulun Lu, Guangji Wang
Summary: This study identifies dioscin as a novel demethylation agent that simultaneously inhibits tumor growth and promotes cardiac function recovery. Dioscin reduces DNMT activities, inhibits breast cancer cell growth, and promotes the expression of antioxidant genes through demethylation. Dioscin exhibits dual functions of anti-cancer and cardio-protection in Nrf2 knockout mice and tumor-bearing mice models.
Article
Biochemical Research Methods
Wenyan Han, Bao-Qing Gao, Junjie Zhu, Zongxing He, Jianfeng Li, Li Yang, Jia Chen
Summary: This article introduces a new gene editing technology, transformer base editor (tBE), which enables efficient base editing without observed off-target mutations. The method can be applied in mammalian cells and mice, and a detailed experimental protocol is provided.
Review
Biochemistry & Molecular Biology
Abdelhakim Bouyahya, Hamza Mechchate, Loubna Oumeslakht, Ikrame Zeouk, Sara Aboulaghras, Abdelaali Balahbib, Gokhan Zengin, Mohammad Amjad Kamal, Monica Gallo, Domenico Montesano, Nasreddine El Omari
Summary: Cancer is a complex disease caused by genetic and epigenetic disruptions in normal cells. Recent studies have shown that natural bioactive compounds can specifically target the epigenome of tumor cells and restore the cellular memory lost during tumor transformation. The use of these substances as anticancer epidrugs is currently an important avenue in cancer research.
Article
Cell Biology
Sandra Alonso-Alonso, Anna Esteve-Codina, Beatriz Martin-Mur, Lucia Alvarez-Gonzalez, Aurora Ruiz-Herrera, Josep Santalo, Elena Ibanez
Summary: Research has found that the derivation rate of embryonic stem cells from single blastomeres of 8-cell mouse embryos is lower, and there are differences in the ability of sister blastomeres to produce ESCs. Although their non-pluripotent fate can be redirected through culture conditions and cell plasticity, at least half of the blastomeres have a lower potential to generate ESCs. Lines originated from the same embryo segregate into two groups based on transcriptional signatures.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Elizabeth M. Corteselli, Mona Sharafi, Robert Hondal, Maximilian MacPherson, Sheryl White, Ying-Wai Lam, Clarissa Gold, Allison M. Manuel, Albert van der Vliet, Severin T. Schneebeli, Vikas Anathy, Jianing Li, Yvonne M. W. Janssen-Heininger
Summary: This study provides insights into the mechanisms of oxidative inactivation of GLRX through molecular modeling and biochemical validation. The study identifies C8 and C83 as target sites for S-glutathionylation and oxidation, with C8 playing a prominent role in dimer formation and aggregation. Combinatorial mutation of C8, C26, and C83 results in increased activity of GLRX and resistance to oxidative inactivation and aggregation.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Moriah Carper, Katherine M. Contreras, D. Matthew Walentiny, Patrick M. Beardsley, M. Imad Damaj
Summary: This study established a mouse model of oxycodone dependence to investigate withdrawal effects, with pretreatment with oxycodone or clonidine preventing emergence of withdrawal signs. Mice treated with oxycodone exhibited more withdrawal signs 24 hours post-injection, while naloxone challenges showed peak withdrawal signs at 6 hours. The model is validated and provides a means to examine novel therapeutics for opioid withdrawal.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Nutrition & Dietetics
Nasreddine El Omari, Saad Bakrim, Mohamed Bakha, Jose M. Lorenzo, Maksim Rebezov, Mohammad Ali Shariati, Sara Aboulaghras, Abdelaali Balahbib, Mars Khayrullin, Abdelhakim Bouyahya
Summary: Cancer is a complex disease with genetic and epigenetic disturbances playing major roles in tumor formation. Research is currently focused on the involvement of epigenetic disturbances in cancer, as well as the effects of drugs on different epigenetic pathways.
Article
Biochemistry & Molecular Biology
Shufeng Ma, Kaitong Liao, Mengrao Li, Xinlong Wang, Jie Lv, Xin Zhang, Hongxin Huang, Lian Li, Tao Huang, Xiaohua Guo, Ying Lin, Zhili Rong
Summary: Liquid-liquid phase separation (LLPS) is utilized to activate gene expression using a droplet-forming CRISPR gene activation system. The system combines the CRISPR-SunTag system with FETIDR-AD fusion proteins, which form phase separation condensates to enhance transcription elongation. The system is compatible with various CRISPR-associated proteins and can activate target genes in mice. This study provides a robust tool for gene expression activation in foundational research and potential therapeutics.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Cameron Hill, Elisabetta Brunello, Luca Fusi, Jesus G. Ovejero, Malcolm Irving
Summary: The study revealed a sequence of structural changes during muscle activation, including thin filament activation, disruption of the helical array of myosin motors, release of myosin motor domains from the folded conformation, and actin attachment. Physiological force generation in skeletal muscle twitch response is limited by incomplete activation of the thick filament and rapid inactivation of both filaments.
Article
Virology
John M. M. Crawford, Liewei L. L. Yan, Hani Zaher, Richard W. W. Hardy
Summary: Virus replication and transmission vary between different hosts. Mosquito-derived Sindbis virus (SINV) replicates and spreads faster in human cells, producing a more infectious virus than its mammalian-derived counterpart. The genomic RNA of mosquito-derived SINV is more efficient in establishing infection in human cells compared to that of mammalian-derived SINV. Host-dependent changes in modification of packaged genomic RNA likely play an important role in SINV infection and replication.
Review
Genetics & Heredity
James P. B. Lloyd, Ryan Lister
Summary: The authors review the intra-individual and inter-individual plant epigenome variation during development and in response to environmental changes, stress included. They also discuss the functions of epigenome plasticity and editing technologies that will drive future research. Advancements in technologies for reading and writing epigenomic patterns are enabling a more detailed characterization and functional interrogation of plant epigenome variation.
NATURE REVIEWS GENETICS
(2022)
Article
Multidisciplinary Sciences
Gavin J. Sutton, Daniel Poppe, Rebecca K. Simmons, Kieran Walsh, Urwah Nawaz, Ryan Lister, Johann A. Gagnon-Bartsch, Irina Voineagu
Summary: Transcriptome deconvolution methods for human brain transcriptome were evaluated and the authors concluded that partial deconvolution algorithms work best, but appropriate cell-type signatures are also important.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
James P. B. Lloyd, Florence Ly, Patrick Gong, Jahnvi Pfluger, Tessa Swain, Christian Pfluger, Elliott Fourie, Muhammad Adil Khan, Brendan N. Kidd, Ryan Lister
Summary: Transcriptional activity in plants is controlled by programmable gene circuits. Synthetic gene circuits have the potential to integrate and customize signals. This study presents a suite of recombinase-based gene circuits for use in plants, which can be used to programmably manipulate transcriptional activity and have stable long-term effects.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell & Tissue Engineering
Christian M. Nefzger, Thierry Jarde, Akanksha Srivastava, Jan Schroeder, Fernando J. Rossello, Katja Horvay, Mirsada Prasko, Jacob M. Paynter, Joseph Chen, Chen-Fang Weng, Yu B. Y. Sun, Xiaodong Liu, Eva Chan, Nikita Deshpande, Xiaoli Chen, Y. Jinhua Li, Jahnvi Pflueger, Rebekah M. Engel, Anja S. Knaupp, Kirill Tsyganov, Susan K. Nilsson, Ryan Lister, Owen J. L. Rackham, Helen E. Abud, Jose M. Polo
Summary: The impact of aging on intestinal stem cells is not fully understood. This study identified widespread epigenetic and transcriptional alterations in old ISCs. Key transcription factors were identified that drive molecular and functional differences between old and young states. These findings contribute to enhancing the regenerative capacity of intestinal stem cells.
NPJ REGENERATIVE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Charles A. Herring, Rebecca K. Simmons, Saskia Freytag, Daniel Poppe, Joel J. D. Moffet, Jahnvi Pflueger, Sam Buckberry, Dulce B. Vargas-Landin, Olivier Clement, Enrique Goni Echeverria, Gavin J. Sutton, Alba Alvarez-Franco, Rui Hou, Christian Pflueger, Kerrie McDonald, Jose M. Polo, Alistair R. R. Forrest, Anna K. Nowak, Irina Voineagu, Luciano Martelotto, Ryan Lister
Summary: This study reveals the dynamic trajectories and regulatory mechanisms of different cell types during human prefrontal cortex development through single-cell resolution analysis of gene expression and chromatin accessibility. The findings provide important clues for understanding neurodevelopment and neurological disorders.
Article
Multidisciplinary Sciences
Patricia Gerdes, Sue Mei Lim, Adam D. Ewing, Michael R. Larcombe, Dorothy Chan, Francisco J. Sanchez-Luque, Lucinda Walker, Alexander L. Carleton, Cini James, Anja S. Knaupp, Patricia E. Carreira, Christian M. Nefzger, Ryan Lister, Sandra R. Richardson, Jose M. Polo, Geoffrey J. Faulkner
Summary: This study investigates the genomic composition and transposon insertions in mouse iPSCs. The researchers find 83 de novo transposable element insertions in miPSCs, with LINE-1 retrotransposons being significantly hypomethylated. Additionally, treatment with the LINE-1 inhibitor lamivudine is shown to block endogenous retrotransposition in miPSCs.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Sally Martin, Daniel Poppe, Nelly Olova, Conor O'Leary, Elena Ivanova, Jahnvi Pflueger, Jennifer Dechka, Rebecca K. K. Simmons, Helen M. M. Cooper, Wolf Reik, Ryan Lister, Ernst J. J. Wolvetang
Summary: DNA methylation is directly related to neuronal genome regulation and maturation. Mouse ESC-derived neurons could recapitulate the in vivo mCH levels over a similar time period. This enables them to be used as a model system to study epigenome maturation over development.
Article
Chemistry, Multidisciplinary
Charlene Waryah, Joseph Cursons, Momeneh Foroutan, Christian Pflueger, Edina Wang, Ramyar Molania, Anabel Sorolla, Christopher Wallis, Colette Moses, Irina Glas, Leandro Magalhaes, Erik W. Thompson, Liam G. Fearnley, Christine L. Chaffer, Melissa Davis, Anthony T. Papenfuss, Andrew Redfern, Ryan Lister, Manel Esteller, Pilar Blancafort
Summary: This work successfully silenced ZEB1 in triple negative breast cancer (TNBC) models through CRISPR/dCas9-mediated epigenetic editing, leading to significant tumor inhibition and the discovery of ZEB1-dependent-signature genes. Epigenetic changes, including reactivation and enhanced chromatin accessibility, were observed in cell adhesion loci, indicating a shift towards a more epithelial state. Silencing of ZEB1 also induced heterochromatin expansion, DNA methylation changes, and chromatin modifications in the ZEB1 promoter. This study demonstrated the potential of epigenome-engineering approaches and customizable precision molecular oncology for targeting poor outcome breast cancers.
Article
Multidisciplinary Sciences
Sam Buckberry, Xiaodong Liu, Daniel Poppe, Jia Ping Tan, Guizhi Sun, Joseph Chen, Trung Viet Nguyen, Alex de Mendoza, Jahnvi Pflueger, Thomas Frazer, Dulce B. Vargas-Landin, Jacob M. Paynter, Nathan Smits, Ning Liu, John F. Ouyang, Fernando J. Rossello, Hun S. Chy, Owen J. L. Rackham, Andrew L. Laslett, James Breen, Geoffrey J. Faulkner, Christian M. Nefzger, Jose M. Polo, Ryan Lister
Summary: Cells undergo a significant epigenome reconfiguration during reprogramming to hiPS cells. The differences in epigenomes between hiPS cells and hES cells affect the function of hiPS cells. Researchers characterized the emergence and persistence of these epigenetic differences and developed a TNT reprogramming strategy that corrects epigenetic memory and aberrations, making hiPS cells more similar to hES cells at a molecular and functional level.
Review
Plant Sciences
Marina Oliva, Ryan Lister
Summary: In recent years, single-cell genomics combined with imaging techniques have become the leading approach in characterizing biological systems. In plant sciences, various tissues and species have been analyzed, providing abundant data on cell identity at a high resolution. This article highlights how single-cell technologies have contributed to our understanding of tissue organization, cell fate dynamics in development or in response to stimuli, and the identification of key regulators of cell identity. It also discusses the challenges, future directions, and potential applications of single-cell omics in understanding, predicting, and manipulating plant development and physiology.
Article
Plant Sciences
Tatsuya Nobori, Marina Oliva, Ryan Lister, Joseph R. Ecker
Summary: PHYTOMap is a multiplexed fluorescence in situ hybridization method that allows for single-cell and spatial analysis of gene expression in whole-mount plant tissue, without the need for transgenes and at a low cost. This study demonstrates the successful application of PHYTOMap in identifying major cell types in Arabidopsis roots and its potential to accelerate the spatial mapping of marker genes in complex plant tissue.
Article
Forestry
Dina Hermawaty, Jonathan Cahn, Ryan Lister, Michael J. Considine
Summary: The regulation of DNA accessibility by histone modification is a key aspect in developmental and environmental programming. In this study, we developed a specific ChIP method for mature dormant buds of grapevine, optimizing every step of the protocol. The analysis of histone H3-enriched DNA successfully evaluated the protocol and identified histone H3 occupancy along grapevine bud chromatin.
Article
Biochemistry & Molecular Biology
Tessa Swain, Christian Pflueger, Saskia Freytag, Daniel Poppe, Jahnvi Pflueger, Trung Viet Nguyen, Ji Kevin Li, Ryan Lister
Summary: The SSSavi system is a modular combinatorial epigenome editing platform that allows precise editing of chromatin contexts by controlling the combination and spatial order of effector recruitment.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Rodrigo Carlessi, Elena Denisenko, Ebru Boslem, Julia Kohn-Gaone, Nathan Main, N. Dianah B. Abu Bakar, Gayatri D. Shirolkar, Matthew Jones, Aaron B. Beasley, Daniel Poppe, Benjamin J. Dwyer, Connie Jackaman, M. Christian Tijam, Ryan Lister, Michael Karin, Jonathan A. Fallowfield, Timothy J. Kendall, Stuart J. Forbes, Elin S. Gray, John K. Olynyk, George Yeoh, Alistair R. R. Forrest, Grant A. Ramm, Mark A. Febbraio, Janina E. E. Tirnitz-Parker
Summary: By using single-nucleus RNA sequencing, researchers identified a disease-associated hepatocyte transcriptional state that is increasingly prevalent in chronic liver disease and associated with structural variants. Integrated analysis of human data confirmed this finding and revealed a correlation between high levels of this hepatocyte transcriptional state and an increased risk of hepatocellular carcinoma development.
Article
Biotechnology & Applied Microbiology
Alex de Mendoza, Trung Viet Nguyen, Ethan Ford, Daniel Poppe, Sam Buckberry, Jahnvi Pflueger, Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alicia Oshlack, Peggy J. Farnham, Pilar Blancafort, Ryan Lister
Summary: Researchers used epigenome engineering techniques to directly test the effect of induced DNA methylation on endogenous promoters. They found that the transcriptional responses to DNA methylation were highly context-specific, and some regulatory networks could override DNA methylation. The study also demonstrated that induced DNA methylation could exist simultaneously with active histone modifications or DNA bound by RNA polymerase II.
