Article
Chemistry, Medicinal
Yasuko Koda, Shin Sato, Hirofumi Yamamoto, Hideaki Niwa, Hisami Watanabe, Chiduru Watanabe, Tomohiro Sato, Kana Nakamura, Akiko Tanaka, Mikako Shirouzu, Teruki Honma, Takehiro Fukami, Hiroo Koyama, Takashi Umehara
Summary: A series of S2157 derivatives were designed, synthesized, and evaluated, with compound 10 showing the most desirable activities and its eutomer S1427 being successfully isolated. S1427 exhibited potent LSD1 inhibitory activity, as well as desirable hERG channel inhibition and microsomal stability.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Min Zhou, Linchang Dai, Chengmin Li, Liuxin Shi, Yan Huang, Zhenqian Guo, Fei Wu, Ping Zhu, Zheng Zhou
Summary: The study explores the specific functions of human histone variants H2A.B and H2A.Z.2.2 in enhancing chromatin dynamics by investigating the structural rearrangements in nucleosome core particles containing these variants. The results reveal how these variants induce unstable nucleosomes and open chromatin structures, shedding light on their critical roles in various biological processes.
Article
Cell Biology
Havell Markus, Jun Zhao, Tania Contente-Cuomo, Michelle D. Stephens, Elizabeth Raupach, Ahuva Odenheimer-Bergman, Sydney Connor, Bradon R. McDonald, Bethine Moore, Elizabeth Hutchins, Marissa McGilvrey, Michelina C. de la Maza, Kendall Van Keuren-Jensen, Patrick Pirrotte, Ajay Goel, Carlos Becerra, Daniel D. Von Hoff, Scott A. Celinski, Pooja Hingorani, Muhammed Murtaza
Summary: Urinary cfDNA fragments exhibit specific patterns of fragmentation, suggesting temporary protection and robustness against preanalytical perturbations. The genome-wide sequencing coverage revealed protected regions conserved across individuals, with potential implications for cancer diagnostics. Furthermore, the fragmentation patterns of urine cfDNA show correlations with gene expression and chromatin accessibility in epithelial cells of the urinary tract, indicating their potential use in cancer diagnostics.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Tianyang Liu, Fiona Shilliday, Alexander D. Cook, Mohammad Zeeshan, Declan Brady, Rita Tewari, Colin J. Sutherland, Anthony J. Roberts, Carolyn A. Moores
Summary: In this study, the authors investigated the role of Plasmodium kinesin-8B in microtubule motility and depolymerization. They found that kinesin-8B is essential for the formation of male gametes and parasite transmission. The study provides important insights into the molecular mechanisms underlying malaria transmission.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Stephanie Portillo-Ledesma, Lucille H. Tsao, Meghna Wagley, Melike Lakadamyali, Maria Pia Cosma, Tamar Schlick
Summary: The study found that chromatin parameters work together to produce nucleosome clutches of different sizes, with the length of nucleosome free regions impacting clutch size and the length of linker DNA having a moderate effect. Higher linker histone densities produce larger clutches through a chromatin compaction mechanism, while higher acetylation levels produce smaller clutches through a chromatin unfolding mechanism.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yunhui Peng, Yaroslav Markov, Alexander Goncearenco, David Landsman, Anna R. Panchenko
Summary: This study comprehensively mapped human histone interaction networks and found limited overlap between networks from different data sources. The analysis revealed scale-free behavior and high modularity of the human histone interactome, with a high number of residues involved in interactions. Additionally, two types of histone binding modes were detected.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biology
Ruben Rosas, Rhiannon R. Aguilar, Nina Arslanovic, Anna Seck, Duncan J. Smith, Jessica K. Tyler, Mair E. A. Churchill
Summary: The histone chaperone CAF-1 deposits histone H3/H4 dimers onto newly replicated DNA to form the central core of the nucleosome tetrasome. The KER SAH region of CAF-1 plays a crucial role in ensuring the assembly of tetrasomes by linking functional domains within CAF-1 with structural precision.
Article
Cell Biology
Maria Alba Abad, Tanmay Gupta, Michael A. Hadders, Amanda Meppelink, J. Pepijn Wopken, Elizabeth Blackburn, Juan Zou, Anjitha Gireesh, Lana Buzuk, David A. Kelly, Toni McHugh, Juri Rappsilber, Susanne M. A. Lens, A. Arockia Jeyaprakash
Summary: It has been discovered that the interaction between Sgo1 and Survivin is crucial for the assembly of CPC-Sgo1 complex. Disrupting the binding between Sgo1 and Survivin disrupts the assembly of CPC-Sgo1 and affects the localization and function of CPC at the centromere. Sgo1 and H3T3ph both interact with the same surface on Survivin to bind CPC.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Nando D. Das, Jen-Chien Chang, Chung-Chau Hon, S. Thomas Kelly, Shinsuke Ito, Marina Lizio, Bogumil Kaczkowski, Hisami Watanabe, Keisuke Katsushima, Atsushi Natsume, Haruhiko Koseki, Yutaka Kondo, Aki Minoda, Takashi Umehara
Summary: This study found that H4K5acK8ac and H3K27ac signals have some overlap in binding to the super-enhancer transcription factor BRD4 at higher levels, but they also have distinct specificities, especially in glioblastoma stem-like cell lines. Deletion of H4K5acK8ac-preferred super-enhancers associated with MYCN and NFIC resulted in a reduction in stem-like properties.
Article
Biochemistry & Molecular Biology
Hongyu Zhao, Xueqin Shao, Mingxin Guo, Yongqiang Xing, Jingyan Wang, Liaofu Luo, Lu Cai
Summary: Nucleosomes are important for eukaryotic chromatin structure and regulate various biological processes. The histone variant H2A.Z can be dynamically incorporated into nucleosomes to modulate gene expression. Researchers have extended a chemical kinetic model to study the assembly dynamics of H2A.Z-containing nucleosomes. They found that the assembly efficiency of H2A.Z-containing nucleosomes is positively correlated with histone octamer concentration, reaction rate constant, and reaction time. Furthermore, they developed a competitive kinetic model to assess the competitive ability of histones in nucleosome assembly and confirmed that H2A has a higher competitive ability than H2A.Z in vitro. This study demonstrates that the assembly of H2A.Z-containing nucleosomes follows chemical kinetic principles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Jiayi Liu, Yu Shangguan, Donge Tang, Yong Dai
Summary: Lysine succinylation is a newly identified histone post-translational modification that influences nucleosomal structure, chromatin dynamics, gene expression, and several diseases. Studies on lysine succinylation of histones are ongoing, highlighting its potential as a target for disease treatment in the future.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Hitoshi Kurumizaka, Tomoya Kujirai, Yoshimasa Takizawa
Summary: Chromatin compacts genomic DNA through nucleosome core particles, with versatile structure and dynamics for epigenetic regulation of genomic DNA. Histone variants in higher eukaryotes contribute to nucleosome diversity and play important roles in chromatin epigenetic regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Simon Obermeyer, Richard Stoeckl, Tobias Schnekenburger, Henna Kapoor, Thomas Stempfl, Uwe Schwartz, Klaus D. Grasser
Summary: In addition to transcriptional initiation, mRNA production is regulated during elongation, and various transcript elongation factors modulate the synthesis of mRNAs by RNA polymerase II (RNAPII) in the chromatin context. TFIIS is an elongation factor that stimulates the transcript cleavage activity of RNAPII, and its deficiency in Arabidopsis plants leads to increased sensitivity to heat stress and decreased expression of heat-induced genes. Further analysis reveals that TFIIS is required for proper RNAPII accumulation at specific nucleosomes and plays a role in reprogramming gene expression for establishing plant thermotolerance.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jinrong Min, Ke Liu
Summary: The dynamic regulation of chromatin structure by various modulators is crucial for downstream DNA processes, and understanding the 3D structures of these modulators in complex with nucleosome is essential for studying chromatin structure changes. Recent progress has been made in structural studies of selected chromatin modulators interacting with nucleosome.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Review
Cell Biology
Yanjing Li, Kexue Ge, Tingting Li, Run Cai, Yong Chen
Summary: This review highlights the recent progress in structural studies of histone lysine methyltransferases (HKMTs), which play important roles in regulating chromatin structure and gene expression. The focus is on representative HKMTs (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases) in complex with nucleosomes, with emphasis on understanding the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these enzymes. These structural studies shed light on the roles of HKMTs in tumorigenesis and provide a basis for developing novel therapeutic approaches targeting HKMTs in cancer.
Review
Biochemistry & Molecular Biology
Kozo Tanaka, Toru Hirota
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2016)
Article
Medicine, Research & Experimental
Motoko Takahashi, Kozo Tanaka, Toshifumi Wakai, Toru Hirota
BIOMEDICAL RESEARCH-TOKYO
(2016)
Article
Gastroenterology & Hepatology
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
Article
Biochemistry & Molecular Biology
Kodai Hara, Shota Taharazako, Masanori Ikeda, Hiroki Fujita, Yoshiko Mikami, Sotaro Kikuchi, Asami Hishiki, Hideshi Yokoyama, Yoshinobu Ishikawa, Shin-ichiro Kanno, Kozo Tanaka, Hiroshi Hashimoto
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Review
Oncology
Kozo Tanaka, Hidemasa Goto, Yuhei Nishimura, Kousuke Kasahara, Akira Mizoguchi, Masaki Inagaki
Article
Multidisciplinary Sciences
Masanori Ikeda, Kozo Tanaka
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Kazuhiko S. K. Uchida, Minji Jo, Kota Nagasaka, Motoko Takahashi, Norihisa Shindo, Katsushi Shibata, Kozo Tanaka, Hiroshi Masumoto, Tatsuo Fukagawa, Toru Hirota
Summary: The spindle-assembly checkpoint delays anaphase onset in response to microtubule vacancy at kinetochores. Kinetochore stretching is found to be essential for checkpoint silencing by promoting PP1 phosphatase recruitment. Lower frequency of kinetochore stretching is associated with prolonged metaphase in cancer cell lines with chromosomal instability.
Article
Cell Biology
Kenji Iemura, Toyoaki Natsume, Kayoko Maehara, Masato T. Kanemaki, Kozo Tanaka
Summary: Most cancer cells exhibit chromosomal instability due to attenuated chromosome oscillation and reduced phosphorylation of Hec1 at serine 55. The regulation of Hec1-S55 phosphorylation by Aurora A through chromosome oscillation is crucial for accurate mitosis. Attenuated chromosome oscillation and reduced Hec1-S55 phosphorylation in cancer cells may lead to chromosome missegregation.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Hironari Nishizawa, Mitsuyo Matsumoto, Guan Chen, Yusho Ishii, Keisuke Tada, Masafumi Onodera, Hiroki Kato, Akihiko Muto, Kozo Tanaka, Kazuhiko Igarashi
Summary: Ferroptotic cells can transfer lipid peroxidation and cell death to surrounding cells, even if the surrounding cells are not exposed to ferroptotic inducers. Ferroptotic cells not only act as dying cells, but also function as signal transmitters inducing a chain of further ferroptosis.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Maho Hino, Kenji Iemura, Masanori Ikeda, Go Itoh, Kozo Tanaka
Summary: Depletion of the mitotic regulator CHAMP1 accelerates mitotic cell death and reduces mitotic slippage, leading to decreased resistance to antimitotic drugs. CHAMP1 plays a role in maintaining Mcl-1 expression, suggesting it can be a target to overcome drug resistance in mitotic cells.
Review
Oncology
Kenji Iemura, Yujiro Yoshizaki, Kinue Kuniyasu, Kozo Tanaka
Summary: Chromosomal instability (CIN) is commonly observed in cancer cells, associated with tumor progression and poor prognosis. Insufficient correction of erroneous kinetochore-microtubule attachments plays pivotal roles in CIN, with chromosome oscillation promoting error correction by phosphorylating Hec1 through Aurora A kinase. Understanding the link between attenuated chromosome oscillation and CIN in cancer cells may provide potential targets for cancer therapy.
Article
Biochemistry & Molecular Biology
Hiroki Fujita, Masanori Ikeda, Ayako Ui, Yunosuke Ouchi, Yoshiko Mikami, Shin-ichiro Kanno, Akira Yasui, Kozo Tanaka
Summary: In the repair of DNA double-strand breaks (DSBs), CHAMP1 and POGZ promote DNA end resection, facilitating homologous recombination (HR), and affect the sensitivity of cells to PARP inhibitors.
Article
Oncology
Kenji Iemura, Hayato Anzawa, Ryo Funayama, Runa Iwakami, Keiko Nakayama, Kengo Kinoshita, Kozo Tanaka
Summary: Most cancer cells exhibit chromosomal instability (CIN), which may be a driving force for tumorigenesis. This study found that high-CIN cells grew more slowly in 2D culture but showed increased tumor formation and growth advantages in 3D culture and in vivo. High-CIN cells had higher karyotype heterogeneity, but this heterogeneity was reduced in formed spheres.
Article
Cell Biology
Guan Chen, Zhenhua Li, Kenji Iemura, Kozo Tanaka
Summary: Chromosomal instability (CIN), characterized by chromosome missegregation and micronucleation, emerges in fibroblasts from aged mice, along with an increased rate of aneuploid cells. This CIN is associated with oxidative stress, as indicated by increased reactive oxygen species and mitochondrial functional decline. Antioxidant treatments reduce CIN by alleviating replication stress and potentially stabilizing microtubules.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Kinue Kuniyasu, Kenji Iemura, Kozo Tanaka
