Review
Oncology
Qiao Li, Qingsan Zhu
Summary: The AlkB family has the ability to catalyze the demethylation of various substrates, regulating gene transcription and expression. Altered methylation of DNA, RNA, and histones is frequently observed in cancer. The AlkB homologs play important roles in cancer genesis, progression, metastasis, and invasion, and may serve as new targets for tumor diagnosis and treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Seohyun Kima, Jin-Sup Park, Jaehoon Lee, Kiseok Keith Lee, Ok-Sun Park, Hee-Seung Choi, Pil Joon Seo, Hyung-Taeg Cho, Jennifer M. Frost, Robert L. Fischer, Yeonhee Choi, Masaru Ohme-Takagi
Summary: The DEMETER (DME) DNA demethylase plays a crucial role in the sporophytic growth and development in Arabidopsis, influencing various aspects of plant growth and development by altering specific gene expression pathways. Its activity affects the transcriptome of developing Arabidopsis plants and may be involved in maintaining stem cell activities during the sporophytic life cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Biochemistry & Molecular Biology
Sergi Aranda, Anna Alcaine-Colet, Cecilia Ballare, Enrique Blanco, Ivano Mocavini, Aleksandra Sparavier, Pedro Vizan, Eva Borras, Eduard Sabido, Luciano Di Croce
Summary: The study found that cell cycle progression in pluripotent cells is influenced by variations in the response to differentiation cues, with the involvement of unknown determinants. The thymine DNA glycosylase (TDG) was identified as a cell-cycle-regulated co-factor of the tumor suppressor p53. It was also discovered that TDG and p53 control the transcription of p53-dependent genes during self-renewal by binding to ESC-specific cis-regulatory elements. Furthermore, TDG plays a crucial role in promoting molecular heterogeneity during the cell cycle and affects cell fate decisions during the early differentiation of mESCs.
Article
Biochemistry & Molecular Biology
Nadine Mueller, Eveliina Ponkkonen, Thomas Carell, Andriy Khobta
Summary: The study reveals that 5-caC may act as a repressory mark to prevent premature activation of promoters, and downstream promoter activation or repression responses are regulated by two separate BER steps where TDG and APE1 act as potential switches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xuelin Zhou, Mengwei Wei, Wenfeng Nie, Yue Xi, Li Peng, Qijie Zheng, Kai Tang, Viswanathan Satheesh, Yuhua Wang, Jinyan Luo, Xuan Du, Rui Liu, Zhenlin Yang, Honggui La, Yingli Zhong, Yu Yang, Jian-Kang Zhu, Jiamu Du, Mingguang Lei
Summary: This study reveals the molecular mechanism of AGDP3 in preventing gene silencing and DNA hypermethylation by binding to the H3K9me2 mark on DNA. The crystal structure analysis shows that AGDP3 anchors dimethylated H3K9 and unmodified H3K4 into different surface pockets, providing insights into its binding specificity.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haotian Zhai, Li Cui, Zhen Xiong, Qingsheng Qi, Jin Hou
Summary: In this study, we developed a CRISPR-mediated protein-tagging signal amplification system for simultaneous multiplexed gene activation and repression in S. cerevisiae, significantly increasing the efficiency of gene regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Plant Sciences
Xiaochun Ding, Xuncheng Liu, Guoxiang Jiang, Zhiwei Li, Yunbo Song, Dandan Zhang, Yueming Jiang, Xuewu Duan
Summary: The study reveals that SlJMJ7 acts as a critical negative regulator of fruit ripening in tomato, regulating the expression of ripening-related genes through the removal of H3K4me3 and DNA demethylation. These findings highlight the importance of the crosstalk between histone methylation and DNA methylation in plant developmental processes.
Review
Oncology
Sannidhi Bhootra, Nandana Jill, Geetha Shanmugam, Sudeshna Rakshit, Koustav Sarkar
Summary: DNA methylation is a major cause of cancer progression, leading to gene silencing or increased mutation probability. Both hypermethylation and hypomethylation play significant roles in oncogenesis, with hypermethylation being more common at CpG islands in gene promoter regions, and hypomethylation occurring globally in genomic sequences. Methylation profiles can aid in cancer detection and treatment.
Article
Multidisciplinary Sciences
Ravi V. Desai, Xinyue Chen, Benjamin Martin, Sonali Chaturvedi, Dong Woo Hwang, Weihan Li, Chen Yu, Sheng Ding, Matt Thomson, Robert H. Singer, Robert A. Coleman, Maike M. K. Hansen, Leor S. Weinberger
Summary: The DNA repair protein Apex1 amplifies transcriptional noise to facilitate cellular reprogramming, originating from shorter-duration, higher-intensity transcriptional bursts generated by Apex1-mediated DNA supercoiling. This mechanism, known as discordant transcription through repair (DiThR), potentiates cellular reprogramming and differentiation by maintaining mean expression levels.
Article
Cell Biology
Baoyu Chen, Yuwen Zhu, Junliang Chen, Yifei Feng, Yong Xu
Summary: This study reveals that differential TCL expression in malignant colorectal cancer cells is associated with histone H3K9 methylation, and the lysine demethylase KDM4B is essential for TCL transcription. KDM4B interacts with the transcription factor ERG1 to activate TCL transcription by facilitating the assembly of pre-initiation complex on the TCL promoter, ultimately influencing migration and invasion of CRC cells. Additionally, upregulation of KDM4B in advanced stage CRC specimens suggests it may serve as a potential therapeutic target for CRC intervention.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Blake A. Caldwell, Monica Yun Liu, Rexxi D. Prasasya, Tong Wang, Jamie E. DeNizio, N. Adrian Leu, Nana Yaa A. Amoh, Christopher Krapp, Yemin Lan, Emily J. Shields, Roberto Bonasio, Christopher J. Lengner, Rahul M. Kohli, Marisa S. Bartolomei
Summary: Active DNA demethylation through TET enzymes is crucial for epigenetic reprogramming in cell state transitions. Biochemically engineered TET mutants that uncouple the oxidation steps of 5mC show distinct roles of 5fC/5caC in somatic cell reprogramming, highlighting their importance in chromatin accessibility changes and DNA demethylation.
Review
Hematology
Andrew B. Das, Carlos C. Smith-Diaz, Margreet C. M. Vissers
Summary: The development of epigenetic therapies has shown promise in diseases like acute myeloid leukemia, but issues such as patient response heterogeneity and resistance may be partly attributed to epigenetic heterogeneity. Combination therapy targeting both driver mutations and epigenetic plasticity could be a key strategy in addressing these challenges.
Article
Biochemistry & Molecular Biology
Luciano Nicosia, Francesca Ludovica Boffo, Elena Ceccacci, Fabio Conforti, Isabella Pallavicini, Fabio Bedin, Roberto Ravasio, Enrico Massignani, Tim C. P. Somervaille, Saverio Minucci, Tiziana Bonaldi
Summary: LSD1 inhibitors MC2580 and DDP-38003 induce AML cell differentiation through downregulation of GSE1 protein, leading to decreased cell viability in vitro and tumor growth in vivo. These inhibitors also upregulate genes associated with immune response and cytokine-signaling pathways by reducing GSE1 binding to their promoters, thus activating transcriptional programs that trigger myeloid differentiation.
Review
Pharmacology & Pharmacy
Chang-Yun Li, Yan-Jun Liu, Fan Tao, Ru-Yi Chen, Jin-Jin Shi, Jian-Fei Lu, Guan -Jun Yang, Jiong Chen
Summary: This article discusses the important role of lysine-specific demethylase 7A (KDM7A) in biological regulation and disease development, as well as its structure, function, and potential drug treatments. KDM7A is not only crucial for normal development but also associated with various diseases.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Physiology
David J. Gregory, Lester Kobzik
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Luuk C. T. Dohmen, Adriana Navas, Deninson Alejandro Vargas, David J. Gregory, Anke Kip, Thomas P. C. Dorlo, Maria Adelaida Gomez
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
David J. Gregory, Igor Kramnik, Lester Kobzik
Article
Chemistry, Analytical
Alan Campion, Kenneth J. Smith, Alexey V. Fedulov, David Z. Gregory, Yuwei Fan, John J. Godleski
ANALYTICAL CHEMISTRY
(2018)
Editorial Material
Critical Care Medicine
David J. Gregory
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2013)
Article
Biochemistry & Molecular Biology
Sanjukta Ghosh, David Gregory, Alexia Smith, Lester Kobzik
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2011)
Article
Biochemistry & Molecular Biology
David J. Gregory, Yiming Zhang, Lester Kobzik, Alexey V. Fedulov
Article
Immunology
David J. Gregory, Marianne Godbout, Irazu Contreras, Genevieve Forget, Martin Olivier
EUROPEAN JOURNAL OF IMMUNOLOGY
(2008)
Article
Multidisciplinary Sciences
Hongwei Zhou, Glen DeLoid, Erica Browning, David J. Gregory, Fengxiao Tan, Alice S. Bedugnis, Amy Imrich, Henry Koziel, Igor Kramnik, Quan Lu, Lester Kobzik
Article
Biochemistry & Molecular Biology
David J. Gregory, Glen M. DeLoid, Sharon L. Salmon, Dennis W. Metzger, Igor Kramnik, Lester Kobzik
Article
Biochemistry & Molecular Biology
Wilfredo F. Garcia-Beltran, Evan C. Lam, Kerri St Denis, Adam D. Nitido, Zeidy H. Garcia, Blake M. Hauser, Jared Feldman, Maia N. Pavlovic, David J. Gregory, Mark C. Poznansky, Alex Sigal, Aaron G. Schmidt, A. John Iafrate, Vivek Naranbhai, Alejandro B. Balazs
Summary: New variants of SARS-CoV-2 show high resistance to vaccine neutralization, with some able to escape vaccine responses with just a few mutations, highlighting the importance of developing broadly protective measures against variants.
Article
Immunology
David J. Gregory, Augustin Vannier, Akiro H. Duey, Tyler J. Roady, Richard K. Dzeng, Maia N. Pavlovic, Michael H. Chapin, Sonia Mukherjee, Hannah Wilmot, Nic Chronos, Richelle C. Charles, Edward T. Ryan, Regina C. LaRocque, Tyler E. Miller, Wilfredo F. Garcia-Beltran, Julia C. Thierauf, A. John Iafrate, Steven Mullenbrock, Mark D. Stump, Randall K. Wetzel, Roberto D. Polakiewicz, Vivek Naranbhai, Mark C. Poznansky
Summary: This study investigated the seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in individuals recovering from COVID-19 or those who have never been infected. The results showed that antibody levels were positively correlated with disease severity, and certain immunogenic peptides were associated with milder illness or protection from symptomatic infection. Cross-reactivity with other coronaviruses was observed, suggesting potential implications for immunity.
Article
Physiology
David J. Gregory, Lester Kobzik, Zhiping Yang, Connor C. McGuire, Alexey V. Fedulov
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2017)
Article
Immunology
David J. Gregory, Robert Sladek, Martin Olivier, Greg Matlashewski
INFECTION AND IMMUNITY
(2008)