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
Multidisciplinary Sciences
Wanlin Jiang, Megan E. Block, Chandra S. Boosani
Summary: This study investigates the role of TNF-alpha and IGF-1 in regulating the epigenetic mechanisms that promote VSMCs proliferation, and identifies a novel molecular mechanism involving DNMT1, HDAC10, and HDAC2. Results reveal the inter-dependence of epigenetic mediators in VSMCs proliferation.
Review
Cell Biology
Eunji Kim, Akash Ahuja, Mi-Yeon Kim, Jae Youl Cho
Summary: Epigenetic regulation plays a crucial role in disease development and progression, as well as in controlling anti-inflammatory and anti-tumor responses. The study highlights the involvement of the activator protein-1 (AP-1) signaling pathway in various cellular processes, and the diverse ways in which methyltransferases modulate AP-1 activities.
Review
Chemistry, Multidisciplinary
Yoshihiro Sohtome, Tadahiro Shimazu, Yoichi Shinkai, Mikiko Sodeoka
Summary: Developing synthetic strategies to construct covalent bonds is a common research topic among synthetic chemists. The success of such strategies relies on the tunability of conditions such as catalysts, reagents, solvents, and reaction temperature. However, controlling chemical reactions in living cells poses challenges due to a smaller number of hit substrates and a complex and inflexible environment. The use of chemical methylome analysis serves as an example of bridging the gap between chemistry and biology in this context.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Cell Biology
Nupur Nigam, Benjamin Bernard, Samantha Sevilla, Sohyoung Kim, Mohd Saleem Dar, Daniel Tsai, Yvette Robbins, Kyunghee Burkitt, Cem Sievers, Clint T. Allen, Richard L. Bennett, Theophilus T. Tettey, Benjamin Carter, Lorenzo Rinaldi, Mark W. Lingen, Houssein Sater, Elijah F. Edmondson, Arfa Moshiri, Abbas Saeed, Hui Cheng, Xiaolin Luo, Kevin Brennan, Vishal Koparde, Chen Chen, Sudipto Das, Thorkell Andresson, Abdalla Abdelmaksoud, Madhavi Murali, Seiji Sakata, Kengo Takeuchi, Raj Chari, Yusuke Nakamura, Ravindra Uppaluri, John B. Sunwoo, Carter Van Waes, Jonathan D. Licht, Gordon L. Hager, Vassiliki Saloura
Summary: We identified SMYD3 as a mediator of immune escape in HPV-negative HNSCC. SMYD3 depletion upregulates type I IFN response and antigen presentation genes in HNSCC cells. Mechanistically, SMYD3 regulates the transcription of UHRF1, which binds to H3K9me3-enriched promoters of immune-related genes and silences their expression.
Review
Cell Biology
Aidan J. Levinsky, Gregor McEdwards, Nasha Sethna, Mark A. Currie
Summary: H3K9 methyltransferases play crucial roles in genome stability, cell type-specific gene expression, and non-histone methylation. They are involved in histone modification and regulate the methylation of various non-histone targets, contributing to genome regulation and cellular functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Urology & Nephrology
Anbarasu Kumaraswamy, Katherine R. Welker Leng, Thomas C. Westbrook, Joel A. Yates, Shuang G. Zhao, Christopher P. Evans, Felix Y. Feng, Todd M. Morgan, Joshi J. Alumkal
Summary: This study systematically reviewed the role of epigenetic factors in prostate cancer from 2015 to 2020, highlighting key preclinical and translational data. Findings from both preclinical and clinical studies were reviewed and summarized, along with a discussion on 12 ongoing clinical studies with epigenetic targeted therapies.
Article
Biochemistry & Molecular Biology
Yuanyuan Yang, Zijian Zhou, Lujia Wang, Peng Gao, Zhong Wu
Summary: The study reveals that G9a and DNMT1 play a key role in the pathogenesis of kidney fibrosis. Inhibiting the expression of G9a and DNMT1 can effectively alleviate fibrosis and alter the expression of key cell cycle regulatory genes and DNA methylation status, thus preventing cell cycle arrest. These findings suggest that simultaneous targeting of G9a and DNMT1 may be a promising strategy for the treatment of kidney fibrosis.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Review
Plant Sciences
Hongmiao Hu, Jiamu Du
Summary: This review focuses on the central role of histone methylation in regulating chromatin state and gene expression in Arabidopsis. It summarizes the current understanding of the dynamic regulation of histone methylation, with a particular emphasis on the histone methyltransferases and demethylases involved.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
Review
Oncology
Jonathan D. Licht, Richard L. Bennett
Summary: Epigenetic therapeutics may deactivate immunosuppressive gene expression or reprogram tumor cells to enhance antigen presentation mechanisms, improving the effectiveness of immunotherapies. Dysregulation of epigenetic mechanisms in cancer may affect the immunogenicity of tumor cells, suggesting the importance of targeting immune evasion in therapeutic strategies.
CLINICAL EPIGENETICS
(2021)
Article
Oncology
Costantine Albany, Zeeshan Fazal, Ratnakar Singh, Emmanuel Bikorimana, Nabil Adra, Nasser H. Hanna, Lawrence H. Einhorn, Susan M. Perkins, George E. Sandusky, Brock C. Christensen, Harold Keer, Fang Fang, Kenneth P. Nephew, Michael J. Spinella
Summary: In patients with platinum-refractory germ cell cancer, the combination of Guadecitabine and cisplatin showed tolerability and demonstrated activity. Some patients achieved partial responses, with complete responses observed in some cases, leading to a clinical benefit rate of 46%.
Article
Biochemistry & Molecular Biology
Svetlana Sharifulina, Valentina Dzreyan, Valeria Guzenko, Svetlana Demyanenko
Summary: The study found that the levels and intracellular localization of DNMT1 and G9a proteins changed in penumbra neurons and astrocytes in the rat cerebral cortex after stroke. Inhibition of DNMT1 and G9a protected penumbra cells from apoptosis and reduced the volume of cerebral infarction induced by stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Cell & Tissue Engineering
Rui Yan, Chan Gu, Di You, Zhongying Huang, Jingjing Qian, Qiuyun Yang, Xin Cheng, Lin Zhang, Hongmei Wang, Ping Wang, Fan Guo
Summary: The research developed a novel single-cell multi-omics sequencing method and found that DNA methylation in human oocytes increases globally during growth, correlating with chromatin accessibility, while specific features of DNA methylation increase with active transcription. Integrated analysis of multi-omics data revealed species-specific gene expression and promoter accessibility contributing to gene body methylation programs.
Article
Urology & Nephrology
Paulina X. Medina X. Rangel, Elizabeth Cross, Chang Liu, Christopher E. E. Pedigo, Xuefei Tian, Elena Gutierrez-Calabres, Soichiro Nagata, Anupama Priyadarshini, Gabriel Lerner, Patricia Bunda, Sudhir Perincheri, Jianlei Gu, Hongyu Zhao, Ying Wang, Kazunori Inoue, Shuta Ishibe
Summary: Loss of Hdac1/2 in podocytes during development leads to sustained DNA damage, senescence, and loss of podocytes. HDACs play a crucial role in maintaining the normal glomerular filtration barrier and preventing premature senescence. The damaged podocytes secrete proinflammatory cytokines, growth factors, and matrix metalloproteinases, resulting in subsequent podocyte detachment and loss.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Toshinori Misaki, Luna Yamaguchi, Jia Sun, Minami Orii, Atsuya Nishiyama, Makoto Nakanishi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Satoshi Ishiyama, Atsuya Nishiyama, Yasushi Saeki, Kei Moritsugu, Daichi Morimoto, Luna Yamaguchi, Naoko Arai, Rumie Matsumura, Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Shintaro Shimamura, Fuyuki Ishikawa, Shoji Tajima, Keiji Tanaka, Mariko Ariyoshi, Masahiro Shirakawa, Mitsunori Ikeguchi, Akinori Kidera, Isao Suetake, Kyohei Arita, Makoto Nakanishi
Article
Multidisciplinary Sciences
Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Atsuya Nishiyama, Christopher B. Mulholland, Sebastian Bultmann, Satomi Kori, Akinori Endo, Yasushi Saeki, Weihua Qin, Carina Trummer, Yoshie Chiba, Haruka Yokoyama, Soichiro Kumamoto, Toru Kawakami, Hironobu Hojo, Genta Nagae, Hiroyuki Aburatani, Keiji Tanaka, Kyohei Arita, Heinrich Leonhardt, Makoto Nakanishi
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Satotaka Omori, Teh-Wei Wang, Yoshikazu Johmura, Tomomi Kanai, Yasuhiro Nakano, Taketomo Kido, Etsuo A. Susaki, Takuya Nakajima, Shigeyuki Shichino, Satoshi Ueha, Manabu Ozawa, Kisho Yokote, Soichiro Kumamoto, Atsuya Nishiyama, Takeharu Sakamoto, Kiyoshi Yamaguchi, Seira Hatakeyama, Eigo Shimizu, Kotoe Katayama, Yasuhiro Yamada, Satoshi Yamazaki, Kanako Iwasaki, Chika Miyoshi, Hiromasa Funato, Masashi Yanagisawa, Hiroo Ueno, Seiya Imoto, Yoichi Furukawa, Nobuaki Yoshida, Kouji Matsushima, Hiroki R. Ueda, Atsushi Miyajima, Makoto Nakanishi
Article
Multidisciplinary Sciences
Christopher B. Mulholland, Atsuya Nishiyama, Joel Ryan, Ryohei Nakamura, Merve Yigit, Ivo M. Glueck, Carina Trummer, Weihua Qin, Michael D. Bartoschek, Franziska R. Traube, Edris Parsa, Enes Ugur, Miha Modic, Aishwarya Acharya, Paul Stolz, Christoph Ziegenhain, Michael Wierer, Wolfgang Enard, Thomas Carell, Don C. Lamb, Hiroyuki Takeda, Makoto Nakanashi, Sebastian Bultmann, Heinrich Leonhardt
NATURE COMMUNICATIONS
(2020)
Correction
Multidisciplinary Sciences
Christopher B. Mulholland, Atsuya Nishiyama, Joel Ryan, Ryohei Nakamura, Merve Yigit, Ivo M. Gluck, Carina Trummer, Weihua Qin, Michael D. Bartoschek, Franziska R. Traube, Edris Parsa, Enes Ugur, Miha Modic, Aishwarya Acharya, Paul Stolz, Christoph Ziegenhain, Michael Wierer, Wolfgang Enard, Thomas Carell, Don C. Lamb, Hiroyuki Takeda, Makoto Nakanishi, Sebastian Bultmann, Heinrich Leonhardt
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Soichiro Kumamoto, Atsuya Nishiyama, Yoshie Chiba, Ryota Miyashita, Chieko Konishi, Yoshiaki Azuma, Makoto Nakanishi
Summary: Studies have shown the essential role of PARP1-HPF1 in LIG3-dependent Okazaki fragment joining, serving as a backup system for when LIG1 is nonfunctional. In the absence of LIG1, LIG3-XRCC1 can be recruited to chromatin for Okazaki fragment joining. Depletion of PARP1 or HPF1 leads to failure in recruiting LIG3 to chromatin, while co-depletion of LIG1 and XRCC1 completely prevents Okazaki fragment joining.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Genetics & Heredity
Atsuya Nishiyama, Makoto Nakanishi
Summary: DNA methylation is a chemical modification that defines cell type and lineage through controlling gene expression and genome stability. Aberrant DNA methylation in cancer cells targets CpG islands in gene expression regulatory elements. Recent studies suggest that the classical model of DNA hypermethylation in cancer needs to be reevaluated.
TRENDS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Satomi Kori, Yuki Shibahashi, Toru Ekimoto, Atsuya Nishiyama, Sae Yoshimi, Kosuke Yamaguchi, Satoru Nagatoishi, Masateru Ohta, Kouhei Tsumoto, Makoto Nakanishi, Pierre-Antoine Defossez, Mitsunori Ikeguchi, Kyohei Arita
Summary: Accumulation of epigenetic alterations is a major cause of tumorigenesis, with drugs targeting DNA methylation-regulating factors showing potential for cancer therapy. UHRF1, essential for DNA methylation maintenance, is overexpressed in cancer cells, making it a promising therapeutic target. The discovery of 5A-DMP as a novel TTD-binding compound and inhibitor of full-length UHRF1:LIG1 interaction suggests potential for future cancer therapy experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
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
Multidisciplinary Sciences
Amika Kikuchi, Hiroki Onoda, Kosuke Yamaguchi, Satomi Kori, Shun Matsuzawa, Yoshie Chiba, Shota Tanimoto, Sae Yoshimi, Hiroki Sato, Atsushi Yamagata, Mikako Shirouzu, Naruhiko Adachi, Jafar Sharif, Haruhiko Koseki, Atsuya Nishiyama, Makoto Nakanishi, Pierre-Antoine Defossez, Kyohei Arita
Summary: In this study, we report the cryo-EM structure of DNMT1 bound to its natural activators, providing a mechanistic basis for DNMT1 activation. The findings reveal a previously unstudied linker playing a key role in the activation process and highlight the importance of this activation mechanism for basic research and drug design.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Ryota Miyashita, Atsuya Nishiyama, Weihua Qin, Yoshie Chiba, Satomi Kori, Norie Kato, Chieko Konishi, Soichiro Kumamoto, Hiroko Kozuka-Hata, Masaaki Oyama, Yoshitaka Kawasoe, Toshiki Tsurimoto, Tatsuro S. Takahashi, Heinrich Leonhardt, Kyohei Arita, Makoto Nakanishi
Summary: The ubiquitin signaling pathway dependent on UHRF1 plays a crucial role in the regulation of maintenance DNA methylation. This study reveals the mechanisms of PAF15 removal from chromatin through deubiquitylation by USP7 and unloading by ATAD5. It also demonstrates the importance of completion of maintenance DNA methylation for the termination of UHRF1-mediated ubiquitin signaling.
Article
Biochemistry & Molecular Biology
Hidetoshi Kajino, Tomomi Nagatani, Miku Oi, Tomoya Kujirai, Hitoshi Kurumizaka, Atsuya Nishiyama, Makoto Nakanishi, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai
RSC CHEMICAL BIOLOGY
(2020)
