Article
Biology
Elitsa Stoyanova, Michael Riad, Anjana Rao, Nathaniel Heintz
Summary: At birth, the mammalian brain contains billions of neurons, which develop into networks and learn adult brain tasks through chemical marks such as methylation and hydroxymethylation. Accumulation of 5hmC, possibly essential for neuronal maturation, highlights the role of Tet proteins in preparing and removing DNA marks. Problematic control of 5hmC levels could potentially contribute to brain disorders, while future studies may provide insights into cancerous cell development due to loss of 5hmC.
Article
Multidisciplinary Sciences
Yibin Liu, Zhiyuan Hu, Jingfei Cheng, Paulina Siejka-Zielinska, Jinfeng Chen, Masato Inoue, Ahmed Ashour Ahmed, Chun-Xiao Song
Summary: Specific and quantitative sequencing of cytosine modifications at base-resolution remains challenging. The authors introduce TAPS beta and CAPS for subtraction-free whole genome sequencing of 5mC and 5hmC.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Sushma Sappa, Debasis Dey, Babu Sudhamalla, Kabirul Islam
Summary: The study explores a unique active site engineering strategy to control catalytic outcomes through modifying enzyme active sites, using TET enzyme as the research target. The findings show that variants with expanded active sites significantly enhance oxidation reactions, while crowded cavities can lead to issues in the catalytic process, and a conserved residue with catalysis-directing ability in the TET family is identified.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Julio C. Flores, Simone Sidoli, Meelad M. Dawlaty
Summary: Tet2 is a member of the Ten-eleven translocation (Tet1/2/3) family of enzymes and plays a role in DNA demethylation and gene regulation in embryonic stem cells. Its catalytic and noncatalytic functions regulate DNA demethylation and Sin3a recruitment at active enhancers in ESCs.
Article
Chemistry, Multidisciplinary
Benjamin J. Mortishire-Smith, Sidney M. Becker, Angela Simeone, Larry Melidis, Shankar Balasubramanian
Summary: Chemical and enzymatic methods are important for studying the distribution and function of epigenetic markers. This study proposes a novel iridium-based treatment that utilizes visible-light photochemistry for direct base conversion in epigenetic sequencing. The reaction involves oxidative quenching and hydrogen atom transfer, leading to the conversion of cytosine derivative to a T-like base. This method shows selectivity for 5-carboxycytosine and can be used in high-throughput detection and diagnostic applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Wenrui Zhong, Jonathan T. Sczepanski
Summary: This article introduces a straightforward approach for constructing stable base excision repair (BER) probes using a unique chimeric d/l-DNA architecture. The chimeric probes have excellent stability within living cells and have been successfully used to monitor relative BER activity, evaluate the efficiency of small molecule BER inhibitors, and study enzyme mutants. The researchers report the first fluorescent probe for real-time monitoring of TDG-mediated BER of 5-formylcytosine and 5-carboxylcytosine in living cells, providing a much-needed tool for studying DNA (de)methylation biology. Chimeric probes offer a robust and highly generalizable approach for real-time monitoring of BER activity in living cells, enabling a broad spectrum of basic research and clinical applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Sona Legartova, Alena Svobodova Kovarikova, Jana Behalova Suchankova, Hana Polasek-Sedlackova, Eva Bartova
Summary: RNA methylation, especially 6-methyladenosine (m(6)A)-modified RNAs, play a specific role in DNA damage response (DDR). In this study, researchers observed that RNA modified at 8-methyladenosine (m(8)A) is recruited to DNA lesions after microirradiation and that this recruitment is PARP dependent. The PARP inhibitor Olaparib prevented adenosine methylation at the damaged chromatin and affected the recognition of lesions by the base excision repair factor XRCC1. The study suggests that modified RNAs likely play a role in the BER mechanism accompanied by active DNA demethylation and that R-loops may represent structures recognized by PARP-dependent non-canonical m(6)A/m(8)A-mediated DNA repair pathway.
Article
Neurosciences
Alec Dick, Alon Chen
Summary: TET proteins play a crucial role in the brain through active demethylation, adapting to environmental stimuli and maintaining dynamic transcription patterns in neurons for neuroplasticity and behavioral adaptation. Research examines the role of TET proteins in stress-induced neuroepigenetic and behavioral adaptations, and potential mechanisms related to stress-related psychiatric disorders.
NEUROBIOLOGY OF STRESS
(2021)
Review
Oncology
Jyoti Shekhawat, Kavya Gauba, Shruti Gupta, Bikram Choudhury, Purvi Purohit, Praveen Sharma, Mithu Banerjee
Summary: TET enzymes play a central role in maintaining methylation balance, and anomalies in their expression may contribute to cancer progression. Low levels of TET enzymes and 5-hmC are associated with tumor invasion, progression, and metastasis. Additionally, the use of vitamin C enhances TET activity.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chirada Dusadeemeelap, Thira Rojasawasthien, Takuma Matsubara, Shoichiro Kokabu, William N. Addison
Summary: This study investigates the role of TET-mediated DNA hydroxymethylation in bone formation using a novel selective TET enzyme inhibitor, BC339. The results show that inhibiting TET with BC339 suppresses osteoblast differentiation and functions through increasing the methylation level of the Sp7 promoter.
Article
Biochemistry & Molecular Biology
Cheng-Gong Liao, Xiao-Hua Liang, Yuan Ke, Li Yao, Man Liu, Ze-Kun Liu, Lin He, Yi-Xiao Guo, Huijie Bian, Zhi-Nan Chen, Ling-Min Kong
Summary: This study reveals that active demethylation of CD147 is involved in the metastasis of non-small cell lung cancer (NSCLC), and targeted methylation of CD147 can inhibit the invasion and metastasis of NSCLC, providing a promising therapeutic target for NSCLC.
Article
Multidisciplinary Sciences
Rafal Rozalski, Daniel Gackowski, Aleksandra Skalska-Bugala, Marta Starczak, Agnieszka Siomek-Gorecka, Ewelina Zarakowska, Martyna Modrzejewska, Tomasz Dziaman, Anna Szpila, Kinga Linowiecka, Jolanta Guz, Justyna Szpotan, Maciej Gawronski, Anna Labejszo, Lidia Gackowska, Marek Foksinski, Elwira Olinska, Aleksandra Wasilow, Andrzej Koltan, Jan Styczynski, Ryszard Olinski
Summary: The study found that levels of active demethylation products in the urine of children with acute lymphoblastic leukemia (ALL) were higher than healthy children, but decreased to healthy levels after chemotherapy. Additionally, the level of 5-hydroxymethylcytosine (5-hmdC) in the DNA of leukocytes was significantly lower in the patient group compared to the control group.
SCIENTIFIC REPORTS
(2021)
Article
Nutrition & Dietetics
Jingwei Liu, Cecile Heraud, Vincent Veron, Jesabel Laithier, Christine Burel, Audrey Prezelin, Stephane Panserat, Lucie Marandel
Summary: Both feeding trials demonstrated that dietary high carbohydrates (dHCs) and low proteins (dLPs) independently induced hepatic global DNA demethylation in trout. The alterations in methylation derivative concentrations suggested an active demethylation pathway, particularly at non-C(m)CGG sites. Hepatic 5-mdC content decreased after refeeding, indicating a potential shift in DNA methylation patterns due to dietary changes.
JOURNAL OF NUTRITION
(2022)
Article
Oncology
Nasim Azizgolshani, Curtis L. Petersen, Youdinghuan Chen, Joshua J. Levy, Lucas A. Salas, Laurent Perreard, Lananh N. Nguyen, Brock C. Christensen
Summary: This study focused on nucleotide-specific 5hmC in pediatric central nervous system tumors, revealing that tumors generally exhibit lower levels of 5hmC throughout the epigenome. The research also demonstrated that tumor 5hmC is localized to key regulatory elements involved in cell identity. Furthermore, differences in hydroxymethylated loci among tumor subtypes were found to be hypermethylated and disproportionately located in CTCF binding sites and genes related to posttranscriptional RNA regulation. Additionally, patients with low 5hmC patterns showed poorer overall survival and higher risk of recurrence.
CLINICAL EPIGENETICS
(2021)
Article
Genetics & Heredity
Chenyan Chang, Ye Yang, Jing Li, Sung-Hyun Park, Guang-chen Fang, Chuan Liang, Weiguo Cao
Summary: This study reveals that the glycosylase SMUG2 from the bacterium Pedobacter heparinus (Phe) has catalytic activity towards both uracil and the oxidative derivatives fC and caC. Mutational and kinetic analyses identified important catalytic residues in Phe SMUG2 and proposed a catalytic model. Structural and catalytic differences between Phe SMUG2 and human TDG were compared through molecular modeling and dynamics simulations.
Letter
Hematology
Daniel Gackowski, Maciej Gawronski, Cassandra Kerr, Tomas Radivoyevitch, Ewelina Zarakowska, Marta Starczak, Abdulkadir Abakir, Alexey Ruzov, Jaroslaw P. Maciejewski, Ryszard Olinski
Article
Genetics & Heredity
Abdulkadir Abakir, Tom C. Giles, Agnese Cristini, Jeremy M. Foster, Nan Dai, Marta Starczak, Alejandro Rubio-Roldan, Miaomiao Li, Maria Eleftheriou, James Crutchley, Luke Flatt, Lorraine Young, Daniel J. Gaffney, Chris Denning, Bjorn Dalhus, Richard D. Emes, Daniel Gackowski, Ivan R. Correa, Jose L. Garcia-Perez, Arne Klungland, Natalia Gromak, Alexey Ruzov
Article
Multidisciplinary Sciences
Igor A. Yakovlev, Daniel Gackowski, Abdulkadir Abakir, Marcos Viejo, Alexey Ruzov, Ryszard Olinski, Marta Starczak, Carl Gunnar Fossdal, Konstantin Krutovsky
SCIENTIFIC REPORTS
(2019)
Editorial Material
Genetics & Heredity
Abdulkadir Abakir, Alexey Ruzov
Article
Biology
Martin J. Blythe, Ayhan Kocer, Alejandro Rubio-Roldan, Tom Giles, Abdulkadir Abakir, Come Ialy-Radio, Lee M. Wheldon, Oxana Bereshchenko, Stefano Bruscoli, Alexander Kondrashov, Joel R. Drevet, Richard D. Emes, Andrew D. Johnson, John R. McCarrey, Daniel Gackowski, Ryszard Olinski, Julie Cocquet, Jose L. Garcia-Perez, Alexey Ruzov
Summary: The study reveals an association between 5-carboxylcytosine (5caC) and LINE-1 retrotransposons activity during murine spermiogenesis, suggesting a potential role of this DNA modification in regulating their transcription.
COMMUNICATIONS BIOLOGY
(2021)
News Item
Biochemistry & Molecular Biology
Abdulkadir Abakir, Wolf Reik
Summary: Sodium bisulfite, a commonly used chemical in methylation sequencing, has limitations as it degrades DNA and cannot distinguish between methylated cytosine and its oxidized derivative, 5-hydroxymethylcytosine. A bisulfite-free technique that involves enzymatic modification of DNA has been developed for direct and accurate methylation mapping.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jan Vijg, Bjoern Schumacher, Abdulkadir Abakir, Michael Antonov, Chris Bradley, Alex Cagan, George Church, Vadim N. Gladyshev, Vera Gorbunova, Alexander Y. Maslov, Wolf Reik, Samim Sharifi, Yousin Suh, Kenneth Walsh
Summary: Genomes are unstable and require constant repair to maintain genetic information. Somatic mutations accumulate in tissues and organs due to errors during genome repair and replication. This article discusses quantitative analysis of somatic mutations, their possible causal role in aging, and options to prevent or eliminate them.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Biochemical Research Methods
Seema Rajani, Christopher Gell, Abdulkadir Abakir, Robert Markus
Summary: This chapter introduces the computational analysis of digital images for comparing and investigating DNA modifications, utilizing fluorescence labeling and confocal microscopy to capture images with precise recording of signals inside the nucleus. It details various analysis methods for visualizing and quantifying DNA modification signals, including investigating co-distribution of signals with dual labeling.
DNA MODIFICATIONS: Methods and Protocols
(2021)
Review
Cell Biology
Ashley Ramsawhook, Alexey Ruzov, Beth Coyle
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2018)
Review
Cell Biology
Peter Jessop, Alexey Ruzov, Martin Gering
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2018)
