Article
Biochemistry & Molecular Biology
Vaidotas Stankevicius, Povilas Gibas, Bernadeta Masiulionyte, Liepa Gasiule, Viktoras Masevicius, Saulius Klimasauskas, Giedrius Vilkaitis
Summary: Enzymatic methylation of cytosine to 5-methylcytosine in DNA is a fundamental epigenetic mechanism involved in mammalian development and disease. In this study, the researchers engineered the Dnmt1 methyltransferase to catalyze the transfer of a synthetic cofactor analog onto DNA. By editing the Dnmt1 locus in mouse embryonic stem cells and using electroporation to introduce the cofactor, they were able to selectively tag Dnmt1-specific genomic targets. This new approach, called Dnmt-TOP-seq, allows for high-resolution tracking of Dnmt1 catalysis in mammalian cells and opens the door for selective studies of other methylation pathways in eukaryotic systems.
Article
Multidisciplinary Sciences
Mirunalini Ravichandran, Dominik Rafalski, Claudia I. Davies, Oscar Ortega-Recalde, Xinsheng Nan, Cassandra R. Glanfield, Annika Kotter, Katarzyna Misztal, Andrew H. Wang, Marek Wojciechowski, Michal Razew, Issam M. Mayyas, Olga Kardailsky, Uwe Schwartz, Krzysztof Zembrzycki, Ian M. Morison, Mark Helm, Dieter Weichenhan, Renata Z. Jurkowska, Felix Krueger, Christoph Plass, Martin Zacharias, Matthias Bochtler, Timothy A. Hore, Tomasz P. Jurkowski
Summary: TET enzymes catalyze the oxidation of 5-methylcytosine bases in DNA and have a strong preference for CGs embedded within transcription factor-binding sites. This preference is determined by intrasubstrate interactions and the flanking CG sequence. The study of TET sequence preferences is physiologically relevant and helps explain the process of DNA demethylation. The most and least favorable TET motifs represent DNA sites bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), shedding light on the function of TET in transcriptional responses and pluripotency support.
Article
Environmental Sciences
Junjie Hu, Yan Yang, Xiaomei Lv, Zhilang Lao, Lili Yu
Summary: The study found that DDT metabolites DDA and DDMU induce DNA hypomethylation by inhibiting DNMT1 activity, leading to changes in the expression of sexual development-related genes.
ENVIRONMENTAL POLLUTION
(2021)
Article
Environmental Sciences
Junjie Quan, Chengwen Ma
Summary: This study reveals a novel regulatory mechanism involving DNMT1-mediated FBXO32 expression in glioma cells, where FBXO32 acts as an E3 ubiquitin ligase to degrade SKP1 via ubiquitination. High FBXO32 expression is associated with improved overall survival in glioma patients and knockdown of DNMT1 in glioma cells increases FBXO32 expression and suppresses malignant phenotypes.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chuck Haggerty, Helene Kretzmer, Christina Riemenschneider, Abhishek Sampath Kumar, Alexandra L. Mattei, Nina Bailly, Judith Gottfreund, Pay Giesselmann, Raha Weigert, Bjoern Braendl, Pascal Giehr, Rene Buschow, Christina Galonska, Ferdinand von Meyenn, Melissa B. Pappalardi, Michael T. McCabe, Lars Wittler, Claudia Giesecke-Thiel, Thorsten Mielke, David Meierhofer, Bernd Timmermann, Franz-Josef Mueller, Joern Walter, Alexander Meissner
Summary: Dnmt1 demonstrates de novo methylation activity with specific targeting towards retrotransposons, depending on Uhrf1. Its genomic recruitment overlaps with regions enriched for Uhrf1, Trim28, and H3K9 trimethylation. These findings suggest that Dnmt1 can catalyze DNA methylation in both de novo and maintenance contexts, particularly at retrotransposons.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Andrea Lauria, Guohua Meng, Valentina Proserpio, Stefania Rapelli, Mara Maldotti, Isabelle Laurence Polignano, Francesca Anselmi, Danny Incarnato, Anna Krepelova, Daniela Donna, Chiara Levra Levron, Giacomo Donati, Ivan Molineris, Francesco Neri, Salvatore Oliviero
Summary: The establishment of DNA methylation patterns during mouse early development is crucial for cell fate determination. However, the specific molecular targets and mechanisms of de novo methylation machinery during differentiation are not fully understood. In this study, the researchers identified DNMT3B-dependent regulatory elements that play a critical role in cell fate determination. They found that DNMT3B-dependent DNA methylation is essential for proper differentiation and lineage determination, and ectopic expression of DNMT3B can restore normal gene expression and cell fate. This study provides important insights into the role of DNA methylation in early development and cell fate determination.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Masaki Kinoshita, Meng Amy Li, Michael Barber, William Mansfield, Sabine Dietmann, Austin Smith
Summary: Genome remethylation is crucial for mammalian development, with a study showing that deficiencies in Dnmt3a and Dnmt3b lead to ES cells developing into trophoblast cells due to failed suppression of Ascl2. Regulating the expression of Ascl2 can impact the transdifferentiation and contribution of ES cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Yanhong Bu, Hong Wu, Ran Deng, Yan Wang
Summary: This study investigated the mechanism of Geniposide (GE) inhibiting angiogenesis in rheumatoid arthritis (RA) and found that GE may inhibit angiogenesis by reducing Dnmt1-mediated PTEN gene hypermethylation, thereby reducing synovitis and angiogenesis in AA rats.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zichen Li, Zebin Tong, Qingyue Gong, Huasong Ai, Shuai Peng, Cong Chen, Guo-Chao Chu, Jia-Bin Li
Summary: Site-selective conjugation chemistry using CAET as a bifunctional handle has been developed to synthesize chemically stable ubiquitin chains. This strategy has been extended to the synthesis of ubiquitinated histones, enabling the study of DNMT1 binding to ubiquitinated nucleosomes and mapping the interaction hotspots. Our work highlights the potential of modern chemical protein synthesis for epigenetic studies.
Article
Gastroenterology & Hepatology
Jianlong Ma, Zhuolin Yang, Zhuofu Huang, Linke Li, Jingliang Huang, Jingying Chen, Rui Ni, Lingfei Luo, Jianbo He
Summary: In end-stage liver diseases, the dysfunctionality of hepatocytes and the scarcity of donor organs make liver transplantation the only curative therapeutic solution. Promoting the transdifferentiation of biliary epithelial cells (BECs) offers a promising treatment, yet the factors governing BEC-derived liver regeneration remain unknown. This study used zebrafish to identify a liver regeneration defect mutant (lrd) and found that the loss of rngtt led to defects in BEC dedifferentiation, progenitor cell activation, and cell proliferation during liver regeneration initiation. The findings suggest that Rngtt is a new factor that initiates BEC-derived liver regeneration.
Review
Biotechnology & Applied Microbiology
Yuchuan Zhou, Chunlin Shao
Summary: Histone methylation plays a crucial role in cellular radiosensitivity by affecting DNA damage repair. Both high and low levels of histone methylation can impede DNA repair processes. Inhibitors of histone methyltransferases and histone demethylases may be helpful in developing new drugs for the therapy of radioresistant tumors.
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
(2021)
Article
Engineering, Environmental
Yibo Zhang, Liu He, Yiqi Yang, Jieqiong Cao, Zijian Su, Bihui Zhang, Huiying Guo, Zhenyu Wang, Peiguang Zhang, Junye Xie, Jieruo Li, Jinshao Ye, Zhengang Zha, Hengyi Yu, An Hong, Xiaojia Chen
Summary: Triclocarban (TCC), a widely used EDC, has been found to cause osteoarthritis (OA) in zebrafish by stimulating the expression of DNMT1 and initiating DNA hypermethylation. This leads to the suppression of type II collagen and other extracellular matrices, resulting in decreased cartilage tissue and narrowing of the intraarticular space, characteristic of OA pathogenesis. The regulation of OA occurrence by TCC is conserved in both zebrafish cartilage tissue and human chondrocytes. DNMT1 is highlighted as a potential therapeutic target for TCC-induced OA.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Xing Wei, Yingxiang Liu, Weijie Hao, Peiwen Feng, Lei Zhang, Hongni Xue, Qunli Zhou, Zekun Guo
Summary: DNA methylation is an important epigenetic modification involved in various biological processes. PGC7 is a maternal factor that maintains DNA methylation during early embryonic development. This study identified a mechanism by which PGC7 regulates genome-wide DNA methylation through the phosphorylation of DNMT1 at ser717 by ERK. These findings provide new insights into DNA methylation-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Iryna Ivasyk, Leonora Olivos-Cisneros, Stephany Valdes-Rodriguez, Marie Droual, Hosung Jang, Robert J. J. Schmitz, Daniel J. C. Kronauer
Summary: While the function of DNA methylation in arthropods is poorly understood, studies in eusocial insects have suggested its role in caste development. However, the findings are inconsistent and controversial. By using CRISPR/Cas9 to mutate DNMT1 in clonal raider ants, the authors demonstrate that ants can undergo normal development without DNMT1 or DNA methylation, contrary to mammals. They also find no evidence of DNA methylation regulating caste development, but show that DNMT1 plays a crucial but unknown role in the insect germline.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Stephanie Chrysanthou, Qin Tang, Joun Lee, Samuel J. Taylor, Yilin Zhao, Ulrich Steidl, Deyou Zheng, Meelad M. Dawlaty
Summary: Research has found that the critical functions of Tet1 in embryonic stem cells and early development are mediated through its non-catalytic roles in regulating H3K27 modifications, which are more important than its catalytic functions in DNA demethylation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
K. Naga Mohan, Ye Cao, Justin Pham, Sau Wai Cheung, Lori Hoffner, Z. Zishuo Ou, Urvashi Surti, Edwin H. Cook, Arthur L. Beaudet
JOURNAL OF HUMAN GENETICS
(2019)
Article
Genetics & Heredity
Sonal Saxena, Poornima Kkani, Chellamuthu Ramasubramanian, Srinivasan Ganesh Kumar, Raghav Monisha, Gundugurti Prasad Rao, Kommu Naga Mohan
ANNALS OF HUMAN GENETICS
(2019)
Article
Multidisciplinary Sciences
Aditya Addepalli, Sakhare Kalyani, Minali Singh, Debashree Bandyopadhyay, K. Naga Mohan
Article
Genetics & Heredity
Sonal Saxena, Sumana Choudhury, Pranay Amruth Maroju, Anuhya Anne, Lov Kumar, Kommu Naga Mohan
Summary: About 50% of dysregulated genes in schizophrenia patients also showed altered transcript levels in neurons with increased DNMT1, independently of DNA methylation. These neurons unexpectedly exhibited genome-wide hypomethylation, along with increased transcript levels of Tet1 and Apobec 1-3 genes, as well as increased activity and copy number of LINE-1 elements. The similarities observed between these neurons and schizophrenia brain samples suggest that DNMT1 overexpression could be a risk factor for schizophrenia.
Article
Genetics & Heredity
Anuhya Anne, Sonal Saxena, Kommu Naga Mohan
Summary: Large DNA methylation changes were found in the gene promoters of cerebellum tissues of patients with autism spectrum disorder (ASD), including genes involved in peroxisome function. This supports the hypothesis that impaired peroxisome function/biogenesis is associated with ASD. Similar approaches could be used to identify rare epimutations in ASD and other complex disorders.
Article
Cell Biology
Anuhya Anne, Lov Kumar, Revanth Kumar K. Salavadi, Pradeep S. S. Anand, Swapna Nuguri, Sukhvinder Bindra, Kanapuram Venkat Ramana Reddy, Gummanur Madhusudhana R. Rao, Kommu Naga N. Mohan
Summary: Oral leukoplakia is a potentially malignant disorder without known genome-scale somatic single nucleotide variant profiles in its hyperplastic/hyperkeratotic stage. Exome sequencing of cases at this stage revealed genetic alterations associated with tobacco chewing, age-related mutation signatures, and dysplasia. Variants in cancer driver genes and those shared with oral dysplasias may contribute to further progression and increased susceptibility to oral cancer.
CYTOGENETIC AND GENOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sonal Saxena, Sumana Choudhury, K. Naga Mohan
Article
Multidisciplinary Sciences
Sonal Saxena, Sumana Choudhury, K. Naga Mohan
