Article
Biochemistry & Molecular Biology
Zhiheng Deng, Huasong Ai, Maoshen Sun, Zebin Tong, Yunxiang Du, Qian Qu, Liying Zhang, Ziyu Xu, Shixian Tao, Qiang Shi, Jia-Bin Li, Man Pan, Lei Liu
Summary: This study elucidates the mechanism of H2B monoubiquitylation and highlights the critical role of nucleosomal DNA in mediating E3 ligase recognition.
Review
Plant Sciences
Jun-Li Wang, Dong-Wei Di, Pan Luo, Li Zhang, Xiao-Feng Li, Guang-Qin Guo, Lei Wu
Summary: This review focuses on the molecular mechanisms through which epigenetic modifications regulate auxin biosynthesis, demonstrating that complex signaling pathways affect gene expression and subsequently protein production.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Cell Biology
Rebekka Karlowitz, Megan L. Stanifer, Jens Roedig, Geoffroy Andrieux, Denisa Bojkova, Marco Bechtel, Sonja Smith, Lisa Kowald, Ralf Schubert, Melanie Boerries, Jindrich Cinatl, Steeve Boulant, Sjoerd J. L. van Wijk
Summary: This study identifies the deubiquitinating enzyme USP22 as a central regulator of basal IFN-λ secretion and SARS-CoV-2 infections in human intestinal epithelial cells. USP22-deficient cells upregulate genes involved in IFN signaling and viral defense, leading to increased IFN-λ secretion and enhanced STAT1 signaling. Interestingly, USP22 controls STING activation and loss of STING reverses STAT activation and ISG and IFN-λ expression. USP22-deficient cells are also protected against SARS-CoV-2 infection in a STING-dependent manner.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Anfeng Luo, Jingwei Kong, Jun Chen, Xue Xiao, Jie Lan, Xiaorong Li, Cuifang Liu, Peng-Ye Wang, Guohong Li, Wei Li, Ping Chen
Summary: This study reveals the mechanism of direct collaboration between ubH2B and FACT at the nucleosome level. The researchers found that ubH2B impairs nucleosome stability and recruits FACT by enhancing its binding on the nucleosome. FACT preferentially binds and deposits H2A-ubH2B dimers to form an intact nucleosome. The stable altered nucleosome state obtained by ubH2B and FACT provides a key platform for gene transcription, as shown by genome-wide and time-course ChIP-qPCR analyses.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Neta Erez, Lena Israitel, Eliya Bitman-Lotan, Wing H. Wong, Gal Raz, Dayanne Cornelio-Parra, Salwa Danial, Na'ama Flint Brodsly, Elena Belova, Oksana Maksimenko, Pavel Georgiev, Todd Druley, Ryan D. Mohan, Amir Orian
Summary: The study reveals that the deubiquitinase Non-stop and Non-stop identity complex (NIC) play crucial roles in regulating the identity of Drosophila midgut enterocytes (ECs), protecting cells from premature aging effects.
Article
Biology
Li Zhang, Pan Luo, Jie Bai, Lei Wu, Dong-Wei Di, Hai-Qing Liu, Jing-Jing Li, Ya-Li Liu, Allah Jurio Khaskheli, Chang-Ming Zhao, Guang-Qin Guo
Summary: The study identified CKRW2 as a mutant form of HUB1 in Arabidopsis, which encodes an E3 ligase required for histone H2B monoubiquitination. The research suggests the involvement of H2Bub1 in regulating auxin biosynthesis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Shu-Ze Zheng, Xiao-Wen Zhang, Xiao-Min Song, Zhuo Yang, Lu Yao, Peng-Fei Tu, Ke-Wu Zeng
Summary: This study discovered a natural small-molecule compound ECL that inhibits microglia-mediated neuroinflammation by editing the monoubiquitination of histone H2B. ECL modifies the previously undisclosed K46 site in H2B and recruits the E3 ubiquitin ligase to promote H2Bub1 at K120, leading to disruption of AP-1 binding to proinflammatory genes in microglia.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Immunology
Nikolaus Dietlein, Xi Wang, Jonas Metz, Olivier Disson, Fuwei Shang, Celine Beyersdoerffer, Esther Rodriguez Correa, Daniel B. Lipka, Yvonne Begus-Nahrmann, Robyn Laura Kosinsky, Steven A. Johnsen, Marc Lecuit, Thomas Hoefer, Hans-Reimer Rodewald
Summary: Emergency hematopoiesis is a response of the immune system aimed at enhancing protection from infection. Research has found that the loss of the deubiquitinase USP22 leads to severe systemic emergency hematopoiesis and increased phagocytosis by neutrophilic granulocytes, ultimately enhancing innate protection against infection.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yangyi Zheng, Sensen Zhang, Yanqiu Luo, Fuquan Li, Jiantao Tan, Bin Wang, Zhe Zhao, Huifang Lin, Tingting Zhang, Jianhong Liu, Xupeng Liu, Jingxin Guo, Xianrong Xie, Letian Chen, Yao-Guang Liu, Zhizhan Chu
Summary: In this study, a new plant-height-related gene, OsUBR7, was identified in rice. Knockout of OsUBR7 resulted in a semi-dwarf phenotype due to a reduction in internode cell number. OsUBR7 encodes a putative E3 ligase that interacts with histones and monoubiquitinates H2B at lysine148. OsUBR7 mediates H2Bub1 at multiple chromatin loci to maintain the normal expression of target genes.
PLANT COMMUNICATIONS
(2022)
Article
Cell Biology
Liying Wang, Zhiliang Xu, Libin Wang, Chao Liu, Huafang Wei, Ruidan Zhang, Yinghong Chen, Lina Wang, Wenwen Liu, Sai Xiao, Wei Li, Wei Li
Summary: The study reveals that RNF20 is crucial for early stage somatic cell reprogramming, with Rnf20 knockout leading to failure in reprogramming at the initial stage. The absence of RNF20 affects the transcription of MET-related genes and early pluripotency genes, ultimately hindering the establishment of a pluripotent gene network.
CELL PROLIFERATION
(2021)
Article
Medicine, Research & Experimental
Adam J. Ferrari, Priyanka Rawat, Hannah S. Rendulich, Akshaya Annapragada, Yasuto Kinose, Xiaoming Zhang, Kyle Devins, Anna Budina, Robert B. Scharpf, Marilyn A. Mitchell, Janos L. Tanyi, Mark A. Morgan, Lauren E. Schwartz, T. Rinda Soong, Victor E. Velculescu, Ronny Drapkin
Summary: Epigenetic aberrations, specifically the loss of histone H2B monoubiquitylation (H2Bub1), are associated with the development and progression of clear cell ovarian carcinoma (CCOC). The study identified hypermethylation of RNF40 as a likely mechanism underlying the loss of H2Bub1 in CCOC. Additionally, depletion of H2Bub1 was found to promote cell proliferation and clonogenicity in an endometriosis cell line.
Editorial Material
Biochemistry & Molecular Biology
Seychelle M. Vos
Summary: A new study has revealed the high-resolution cryo-EM structure of the human SAGA complex, shedding light on its role in different stages of eukaryotic transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Genetics & Heredity
Anna Schmuecker, Bingkun Lei, Zdravko J. Lorkovic, Matias Capella, Sigurd Braun, Pierre Bourguet, Olivier Mathieu, Karl Mechtler, Frederic Berger
Summary: The selection of C-terminal motifs contributes to the evolution of distinct histone H2A variants, with cell cycle dependent kinases playing a crucial role. Interference between the functions carried by these motifs led to their mutual exclusion and the evolution of different classes of H2A variants.
Review
Plant Sciences
Rocio Nunez-Vazquez, Benedicte Desvoyes, Crisanto Gutierrez
Summary: Plants have developed various mechanisms to adapt to abiotic stresses, which involve transcriptional regulation and chromatin modifications. Understanding and manipulating these regulatory networks are crucial for enhancing crop resilience and performance against stress.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Nathan J. VanDusen, Julianna Y. Lee, Weiliang Gu, Catalina E. Butler, Isha Sethi, Yanjiang Zheng, Justin S. King, Pingzhu Zhou, Shengbao Suo, Yuxuan Guo, Qing Ma, Guo-Cheng Yuan, William William Pu
Summary: The study utilized in vivo somatic Cas9 mutagenesis in mice to conduct a forward genetic screen for regulators of cardiomyocyte maturation, identifying transcriptional regulators such as RNF20 and RNF40. Mechanistic studies showed that these regulators control dynamic gene expression changes essential for cardiomyocyte maturation.
NATURE COMMUNICATIONS
(2021)
Article
Psychology, Developmental
Sarah M. Merrill, Nicole Gladish, Maggie P. Fu, Sarah R. Moore, Chaini Konwar, Gerald F. Giesbrecht, Julia L. MacIssac, Michael S. Kobor, Nicole L. Letourneau
Summary: Attachment is a motivational system that promotes felt security to a caregiver, leading to a persistent internal working model of interpersonal behavior. Attachment styles are developed in early social environments and can predict future health and development outcomes. This study found that infant DNA methylation is associated with toddler attachment styles. Additionally, certain DNA methylation sites were found to be related to proinflammatory immune phenotypes and cognitive development.
ATTACHMENT & HUMAN DEVELOPMENT
(2023)
Article
Obstetrics & Gynecology
Sarah R. Moore, Sarah M. Merrill, Bikram Sekhon, Julia L. MacIsaac, Michael S. Kobor, Gerald F. Giesbrecht, Nicole Letourneau
Summary: Exposure to adverse childhood experiences can increase the risk for mental and physical health issues, with intergenerational transmission playing a role in predicting health problems in future generations. Analysis of DNA methylation patterns in infants suggests a potential link to maternal adverse childhood experiences, with a stronger influence observed in blood samples compared to buccal epithelial cells. Influences of maternal distress and cortisol levels on these associations were also explored, indicating a complex interplay between maternal factors and infant DNA methylation patterns.
EARLY HUMAN DEVELOPMENT
(2022)
Article
Endocrinology & Metabolism
Ives Yubin Lim, Xinyi Lin, Ai Ling Teh, Yonghui Wu, Li Chen, Menglan He, Shiao-Yng Chan, Julia L. MacIsaac, Jerry K. Y. Chan, Kok Hian Tan, Mary Foong Fong Chong, Michael S. Kobor, Keith M. Godfrey, Michael J. Meaney, Yung Seng Lee, Johan G. Eriksson, Peter D. Gluckman, Yap Seng Chong, Neerja Karnani
Summary: Antenatal hyperglycemia is associated with increased risk of adverse health outcomes in both mother and child. This study found that variations in maternal glucose levels during pregnancy can affect offspring cord tissue DNA methylation, with different impacts on the child's health.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Neurosciences
Eva Haas, Rana D. Incebacak, Thomas Hentrich, Chrisovalantou Huridou, Thorsten Schmidt, Nicolas Casadei, Yacine Maringer, Carola Bahl, Frank Zimmermann, James D. Mills, Eleonora Aronica, Olaf Riess, Julia M. Schulze-Hentrich, Jeannette Huebener-Schmid
Summary: The study presented a new mouse model mimicking Spinocerebellar ataxia type 3, characterized by neuropathological and behavioral features, and showing similar gene expression perturbances at the transcriptional level to human SCA3 patients.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Psychiatry
Anke Huls, Catherine J. Wedderburn, Nynke A. Groenewold, Nicole Gladish, Meaghan J. Jones, Nastassja Koen, Julia L. MacIsaac, David T. S. Lin, Katia E. Ramadori, Michael P. Epstein, Kirsten A. Donald, Michael S. Kobor, Heather J. Zar, Dan J. Stein
Summary: This study analyzed the associations between newborn DNA methylation (DNAm), neonatal magnetic resonance imaging (MRI) neuroimaging data, and neurodevelopment. The results showed that differential DNAm and increased neonatal caudate volumes were independently associated with severe neurodevelopmental delay. This suggests that neurobiological signals for severe developmental delay may be detectable in very early life.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2022)
Article
Cell Biology
Sara Y. Brucker, Thomas Hentrich, Julia M. Schulze-Hentrich, Martin Pietzsch, Noel Wajngarten, Anjali Ralhan Singh, Katharina Rall, Andre Koch
Summary: MRKH syndrome is a condition characterized by the underdevelopment of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still unknown and current research has been focused on DNA sequencing efforts. However, the development of long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients has provided insights into potential disease-causing pathways and treatment opportunities.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Samantha L. Schaffner, Zinah Wassouf, Diana F. Lazaro, Mary Xylaki, Nicole Gladish, David T. S. Lin, Julia MacIsaac, Katia Ramadori, Thomas Hentrich, Julia M. Schulze-Hentrich, Tiago F. Outeiro, Michael S. Kobor
Summary: This study identified the association between alpha-synuclein variants and epigenetic regulation of PD, impacting DNA methylation at thousands of CpGs and DNA hydroxymethylation at hundreds of CpGs, primarily involving genes related to locomotor behavior and glutamate signaling pathways.
HUMAN MOLECULAR GENETICS
(2022)
Article
Cell Biology
Celine Posseme, Alba Llibre, Bruno Charbit, Vincent Bondet, Vincent Rouilly, Violaine Saint-Andre, Jeremy Boussier, Jacob Bergstedt, Nikaia Smith, Liam Townsend, Jamie A. Sugrue, Cliona Ni Cheallaigh, Niall Conlon, Maxime Rotival, Michael S. Kobor, Estelle Mottez, Stanislas Pol, Etienne Patin, Matthew L. Albert, Lluis Quintana-Murci, Darragh Duffy
Summary: We found that interferon beta is a major determinant of IL-12p70 production induced by lipopolysaccharide and is associated with circulating monocytes. Reduced IFN beta-IL-12p70 responses were observed in patients with SARS-CoV-2 infection or chronic HCV infection, and these responses were resolved after viral clearance. This study provides important insights into the roles of IL-12p70 and IFN beta in healthy and infected individuals and how genetic and epigenetic variation may impact immune responses to bacterial infection.
Article
Oncology
Calen P. Ryan, Raviraj J. Rege, Nanette R. Lee, Delia B. Carba, Michael S. Kobor, Julie L. MacIsaac, David S. Lin, Parmida Atashzay, Christopher W. Kuzawa
Summary: This study aims to explore the relationship between maternal epigenetic age and birth outcomes. Using a sample of Filipino women, the results showed that only one relationship among the multiple dimensions of epigenetic clocks was significantly associated with gestational age at delivery.
CLINICAL EPIGENETICS
(2022)
Article
Biochemistry & Molecular Biology
Alexander Kilzheimer, Thomas Hentrich, Carola Rotermund, Philipp J. Kahle, Julia M. Schulze-Hentrich
Summary: The effect of nutrition on the pathology of Parkinson's disease (PD) and its underlying molecular mechanisms are still unclear. This study used an alpha-synuclein transgenic mouse model and found that a high-fat diet accelerated the development of PD, potentially due to the failure of metabolic adaptions.
HUMAN MOLECULAR GENETICS
(2023)
Article
Psychology, Biological
Roseriet Beijers, Ilse ten Thije, Emma Bolhuis, Kieran J. O'Donnell, Marieke S. Tollenaar, Idan Shalev, Waylon J. Hastings, Julia L. MacIsaac, David T. S. Lin, Michael Meaney, Michael S. Kobor, Jay Belsky, Carolina de Weerth
Summary: This study examines the association between childhood stressor exposure and negative mental and physical health outcomes in later life through cellular aging. The results show that there is no significant impact of childhood risk exposure on cellular aging in a Dutch low-risk community sample. The study also finds a positive correlation between telomere length and cortisol reactivity at age 6, which warrants further investigation.
Article
Medicine, General & Internal
Rebecca Buchert, Elisabeth Schenk, Thomas Hentrich, Nico Weber, Katharina Rall, Marc Sturm, Oliver Kohlbacher, Andre Koch, Olaf Riess, Sara Y. Brucker, Julia M. Schulze-Hentrich
Summary: By analyzing the genetic material of discordant monozygotic twins with MRKH, potential genetic causes were identified. The study revealed the involvement of estrogen in the pathology of MRKH, although no clear pathogenic differences were detected.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Psychiatry
Susanne Edelmann, Ariane Wiegand, Thomas Hentrich, Sarah Pasche, Julia Maria Schulze-Hentrich, Matthias H. J. Munk, Andreas J. Fallgatter, Benjamin Kreifelts, Vanessa Nieratschker
Summary: Social anxiety disorder (SAD) is characterized by severe fear and avoidance in social situations. Early life adversity (ELA) is a major risk factor for SAD, leading to structural and regulatory alterations that contribute to disease vulnerability. However, the molecular link between ELA and adult SAD remains unclear.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Environmental Sciences
Poojitha Rajasekar, Robert J. Hall, K. C. Binaya, Parth S. Mahapatra, Siva P. Puppala, Dhruma Thakker, Julia L. Macisaac, David Lin, Michael Kobor, Charlotte E. Bolton, Ian Sayers, Ian P. Hall, Rachel L. Clifford
Summary: Household air pollution caused by inefficient cooking practices leads to 4 million deaths annually worldwide. This study aimed to investigate the molecular mechanisms of lung disease induced by cook stove smoke exposure. By exposing human airway epithelial cells to different cookstove and fuel types, the researchers identified changes in gene expression, DNA methylation, and hydroxymethylation. They found that traditional cook stove smoke caused oxidative stress and different cook stove smoke types had distinct effects on DNA methylation and hydroxymethylation. These findings provide further insight into the association between indoor air pollution exposure and chronic lung disease mechanisms.
ENVIRONMENTAL POLLUTION
(2023)