Article
Biochemical Research Methods
Kazi Morshed Alom, Young Jun Seo
Summary: In this report, a method for selective and sensitive detection of methyl transferase activity is presented. This method utilizes a dsDNA probe with C3 spacers and dUThioTP-TdT polymerase-based poly-tailing. The probe contains a methyl transferase recognition sequence that can be methylated, unblocking the probe into two separate dsDNA forms with exposed 3' OH groups. This unblocked probe is then subjected to fluorescent dUThioTP-based tailing, producing a strong fluorescent signal indicating the presence of methyl transferase activity.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biology
Shan Qi, Javier Mota, Siu-Hong Chan, Johanna Villarreal, Nan Dai, Shailee Arya, Robert A. Hromas, Manjeet K. Rao, Ivan R. Correa, Yogesh K. Gupta
Summary: The METTL3-METTL14 complex catalyzes methylation of RNA and DNA, with a preference for single-stranded DNA and structured RNA, respectively. The complex has a higher affinity for structured RNA but methylates RNA less efficiently than DNA. Furthermore, the methylation of DNA by the complex is restricted by structured RNA elements prevalent in cellular RNAs.
Review
Pharmacology & Pharmacy
Zhixiong Zhang, Guan Wang, Yuyan Li, Dongsheng Lei, Jin Xiang, Liang Ouyang, Yanyan Wang, Jinliang Yang
Summary: DNA methylation is an important epigenetic process that regulates gene expression and has become a promising target for cancer treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Analytical
Zhen Liu, Keyun Wang, Mingliang Ye
Summary: In order to understand the function of protein arginine methyltransferases(PRMTs), it is crucial to identify their substrate proteins. However, this is challenging due to the dominance of stable and strong interacting proteins over weak and transient substrate proteins. In this study, a novel photoreactive probe-based strategy was developed to identify the substrate proteins of methyltransferases, specifically PRMT1. This strategy effectively distinguished substrate proteins from other interacting proteins and allowed the identification of highly confident substrate proteins. Importantly, it was discovered that hypomethylation of proteins is a prerequisite for efficient capturing of substrate proteins. This study describes the development of a robust chemical proteomic tool for profiling transient substrates and has broad biomedical applications.
ANALYTICAL CHEMISTRY
(2023)
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
Medicine, Research & Experimental
Juan Ramon Tejedor, Clara Bueno, Meritxell Vinyoles, Paolo Petazzi, Antonio Agraz-Doblas, Isabel Cobo, Raul Torres-Ruiz, Gustavo F. Bayon, Raul F. Perez, Sara Lopez-Tamargo, Francisco Gutierrez-Aguera, Pablo Santamarina-Ojeda, Manuel Ramirez-Orellana, Michela Bardini, Giovanni Cazzaniga, Paola Ballerini, Pauline Schneider, Ronald W. Stam, Ignacio Varela, Mario F. Fraga, Agustin F. Fernandez, Pablo Menendez
Summary: B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with infant B-ALL (iB-ALL) showing unique DNA mutational landscape and potential epigenetic mechanisms contributing to leukemogenesis. Integrated analysis of methylome and transcriptome data from MLLr and non-MLLr iB-ALL patients revealed chromatin state alterations and identified distinct gene expression patterns, particularly related to the AP-1 complex and RUNX factors in MLLr iB-ALL. Pharmacological inhibition of AP-1 showed promising potential in impairing MLLr-leukemic growth, suggesting a novel therapeutic approach for MLLr-iB-ALL.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Chemistry, Analytical
Cuiying Lin, Qingqing Huang, Mengjian Tian, Fang Luo, Jian Wang, Bin Qiu, Shuofei Yang, Zhenyu Lin
Summary: An electrochemiluminescence (ECL) biosensor with dual signal enhancement was developed to detect DNA adenine methylation methyltransferase (Dam MTase). The biosensor utilized a restriction endonuclease to cleave DNA and activate CRISPR/Cas12a trans-cleavage activity, resulting in enhanced ECL signal. The biosensor exhibited a good linear relationship with Dam MTase concentration and was successfully applied for detection in serum samples.
Article
Medicine, General & Internal
Katarina Lopusna, Pawel Nowialis, Jana Opavska, Ajay Abraham, Alberto Riva, Rene Opavsky
Summary: The study revealed that Dnmt3b's catalytic activity is largely dispensable for mouse development but critical for preventing tumorigenesis by controlling events involved in cellular transformation. The lack of Dnmt3b's catalytic activity promoted fibroblast transformation in vitro and accelerated the development of certain types of leukemia and lymphoma in vivo.
Article
Biotechnology & Applied Microbiology
Thanvi Srikant, Wei Yuan, Kenneth Wayne Berendzen, Adrian Contreras-Garrido, Hajk-Georg Drost, Rebecca Schwab, Detlef Weigel
Summary: A systematic analysis of the requirement for MET1 in different A. thaliana accessions reveals that CG methylation plays a dual role in gene expression. For many genes, CG methylation appears to canalize expression levels, masking regulatory divergence. However, for a smaller subset of genes, CG methylation increases expression diversity beyond genetically encoded differences.
Review
Biochemistry & Molecular Biology
Young-Su Yi
Summary: Inflammasome, activated in response to infection and damage, triggers inflammatory responses, while methylation, a critical biological process, modulates gene expression. The functional relationship between inflammasome regulation and methylation may play a key role in inflammatory responses and disease development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Konstantinos Koudounas, Gregory Guirimand, Luisa Fernanda Rojas Hoyos, Ines Carqueijeiro, Pamela Lemos Cruz, Emily Stander, Natalja Kulagina, Jennifer Perrin, Audrey Oudin, Sebastien Besseau, Arnaud Lanoue, Lucia Atehortua, Benoit St-Pierre, Nathalie Giglioli-Guivarc'h, Nicolas Papon, Sarah E. O'Connor, Vincent Courdavault
Summary: Many plant species from the Apocynaceae, Loganiaceae and Rubiaceae families produce a variety of monoterpene indole alkaloids (MIAs) which have pharmacological properties. The subcellular localization of N-methyltransferases (NMTs) in MIA-producing plants adds a new layer of complexity to the biosynthetic pathway.
PLANT AND CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena Belova, Oksana Maksimenko, Pavel Georgiev, Artem Bonchuk
Summary: The presence of a conserved proline residue in Kaiso protein and its cis-conformation play crucial roles in efficient DNA binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim
Summary: This study reveals unprecedented insights into the structure and function of CP2c, providing clues for its transcriptional regulation mechanism and potential therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Yiping Hu, Bihua Xu, Juan He, Hongying Shan, Gengmin Zhou, Deli Wang, Lu Bai, Hongxi Shang, Liping Nie, Fan Pan, Hui Yao Lan, Qingwen Wang
Summary: This study found that the expression of Smad7 was significantly decreased in CD4(+) T cells of rheumatoid arthritis (RA) patients and inversely correlated with clinical parameters of RA. DNA hypermethylation in the Smad7 promoter region was observed in CD4(+) T cells of RA patients. These findings suggest that the loss of Smad7 expression and DNA hypermethylation may contribute to the disease activity of RA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Chuan Zhang, Lu Wang, Chi Jin, Jiahui Zhou, Chaofan Peng, Yong Wang, Ziwei Xu, Dongsheng Zhang, Yuanjian Huang, Yue Zhang, Dongjian Ji, Wen Peng, Kangpeng Jin, Junwei Tang, Yifei Feng, Yueming Sun
Summary: Colorectal cancer is a common cancer worldwide, with liver metastasis being a key factor affecting prognosis. A study revealed that Lnc-LALC can regulate CRC cell metastasis ability by affecting DNA methylation status, highlighting its important role in CRLM.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Yoshimi Yasukawa, Naoko Hattori, Naoko Iida, Hideyuki Takeshima, Masahiro Maeda, Tohru Kiyono, Shigeki Sekine, Yasuyuki Seto, Toshikazu Ushijima
Summary: The study identified SAA1 as a potential therapeutic target from primary gastric CAFs, with its upregulation likely mediated by enhancer activation. Experimental results showed that overexpression of SAA1 can enhance the migration ability of gastric cancer cells, indicating its important role in gastric cancer growth.
Article
Biochemistry & Molecular Biology
Rei Tohda, Hideaki Tanaka, Risa Mutoh, Xuhong Zhang, Young-Ho Lee, Tsuyoshi Konuma, Takahisa Ikegami, Catharina T. Migita, Genji Kurisu
Summary: The study solves the high-resolution crystal structure of soybean HO-1, revealing novel structural components and proposing evolutionary fine-tuning of plant-type HOs for ferredoxin dependency to adapt to dynamic pH changes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Chun-Dong Zhang, Hideyuki Takeshima, Shigeki Sekine, Satoshi Yamashita, Yu-Yu Liu, Naoko Hattori, Hiroyuki Abe, Hiroharu Yamashita, Masahide Fukuda, Yu Imamura, Tetsuo Ushiku, Hitoshi Katai, Hiroshi Makino, Masayuki Watanabe, Yasuyuki Seto, Toshikazu Ushijima
Summary: The study aimed to develop a marker for predicting the tissue origin of esophagogastric junction adenocarcinomas based on DNA methylation profiles, identifying two highly specific GAC markers. These markers successfully predicted the tissue origin of EGJ adenocarcinoma in FFPE samples.
Article
Oncology
Naoko Hattori, Kiyoshi Asada, Nozomu Miyajima, Akiko Mori, Yoko Nakanishi, Kana Kimura, Mika Wakabayashi, Hideyuki Takeshima, Chika Nitani, Junichi Hara, Toshikazu Ushijima
Summary: The study demonstrated that epigenetic drug-based differentiation therapy using 5-aza-dC and TBT is a promising strategy for refractory NBLs. Tamibarotene monotherapy induces tumor regression in vivo, while 5-aza-dC monotherapy induces demethylation of NBL-related genes. The combination of these two drugs enhances the therapeutic effect on NBL.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Summary: This study aimed to identify markers for evaluating ovarian cancer cell fraction. Using genome-wide DNA methylation data, SIM1 and ZNF154 were found to be highly correlated with pathological cancer cell fractions. Pyrosequencing primers were successfully designed for cost-effective analysis. In an independent validation cohort, ZNF154 methylation showed a significant correlation with the pathological cancer cell fraction.
Article
Multidisciplinary Sciences
Sho Tsuyuki, Hideyuki Takeshima, Shigeki Sekine, Yukinori Yamagata, Takayuki Ando, Satoshi Yamashita, Shin Maeda, Takaki Yoshikawa, Toshikazu Ushijima
Summary: Analysis showed that gastric cancers with current and past H. pylori infection had similar profiles of genetic alterations in terms of point mutations and gene amplification.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Article
Chemistry, Multidisciplinary
Yasuto Todokoro, Su-Jin Kang, Toshiharu Suzuki, Takahisa Ikegami, Masatsune Kainosho, Masasuke Yoshida, Toshimichi Fujiwara, Hideo Akutsu
Summary: Proton translocation through the Fo component of F-type ATP synthase is facilitated by the rotation of the c-subunit ring. The study determined the chemical conformation of essential acidic residues in the c-ring and elucidated a unique proton translocation mechanism. These findings provide insights into ATP synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Sho Uedaa, Satoshi Yamashita, Miho Nakajima, Tadashi Kumamoto, Chitose Ogawa, Yu-Yu Liu, Harumi Yamada, Emi Kubo, Naoko Hattori, Hideyuki Takeshima, Mika Wakabayashi, Naoko Iida, Yuichi Shiraishi, Masayuki Noguchi, Yukio Sato, Toshikazu Ushijima
Summary: This study developed a cost-effective pipeline called EcoSeq, which utilizes duplex sequencing to accurately count somatic mutations in single DNA molecules. The researchers used this method to analyze normal blood cells from pediatric sarcoma patients and found that the mutation frequency significantly increased in patients who received chemotherapy, with the increased frequency persisting even months after chemotherapy. This suggests that mutation accumulation poses a risk of secondary leukemia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Summary: A quantitative method was established to evaluate the DNA methylation level of the immediate upstream region of major BRCA1 transcriptional start sites (TSSs). The methylation of this region was found to be an independent favorable prognostic factor in high-grade serous ovarian cancer patients.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Keiichi Hata, Naohiro Kobayashi, Keita Sugimura, Weihua Qin, Deis Haxholli, Yoshie Chiba, Sae Yoshimi, Gosuke Hayashi, Hiroki Onoda, Takahisa Ikegami, Christopher B. Mulholland, Atsuya Nishiyama, Makoto Nakanishi, Heinrich Leonhardt, Tsuyoshi Konuma, Kyohei Arita
Summary: This study determined the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. The results showed that DPPA3 induces alpha-helices upon binding to UHRF1 PHD, leading to stable complex formation through multifaceted interactions. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibit the binding of UHRF1 and its chromatin localization.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Takatsune Shimizu, Eiji Sugihara, Hideyuki Takeshima, Hiroyuki Nobusue, Rui Yamaguchi, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Toshikazu Ushijima, Akihiro Muto, Hideyuki Saya
Summary: Mutant p53 in osteosarcoma cells does not suppress the activity of wild-type p53. Targeting mutant p53 R270C (equivalent to human R273C) has limited therapeutic potential, as it does not prevent invasion and metastasis in cells.
Article
Cell & Tissue Engineering
Luisa H. Andrade H. da Silva, Rachel A. A. Heuer, Christian B. B. Roque, Tammy L. L. McGuire, Tomonori Hosoya, Hironobu Kimura, Kouichi Tamura, Akihiro J. J. Matsuoka
Summary: Stem cell replacement shows potential for treating sensorineural hearing loss (SNHL). Immune evasion strategies can improve the survival and residence time of transplanted stem cells in the cochlea, leading to better outcomes.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Oncology
Nobuaki Arai, Naoko Hattori, Satoshi Yamashita, Yu-Yu Liu, Takahiro Ebata, Chihiro Takeuchi, Hideyuki Takeshima, Satoshi Fujii, Haruhiko Kondo, Hirofumi Mukai, Toshikazu Ushijima
Summary: The aim of this study was to explore the methylation-silencing mechanism of the HSD17B4 gene in HER2-positive breast cancer. Knocking out the HSD17B4 gene led to suppressed cell proliferation, enhanced sensitivity to lapatinib, accumulation of VLCFA, decrease in polyunsaturated fatty acids, increased Akt phosphorylation, and upregulation of genes involved in oxidative phosphorylation and electron transport chain.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Biochemical Research Methods
Tsuyoshi Konuma, Jun-ichi Kurita, Takahisa Ikegami
Summary: The relaxation dispersion (rd) of nuclear magnetic resonance provides thermodynamic and kinetic information for molecules with exchanging conformations. We developed a new pulse sequence (AFTAC) that can suppress artifacts in magnetization components and demonstrated its effectiveness in measuring methyl groups. The AFTAC method achieves similar artifact suppression quality in SI, SI2, and SI3 spin systems.
JOURNAL OF MAGNETIC RESONANCE
(2023)