Article
Multidisciplinary Sciences
Xinghong Guo, Kai Liang, Longqing Xia, Xu Zhang, Jinbo Liu, Chuan Wang, Jinquan Li, Xiangzhi Li, Xinguo Hou, Li Chen
Summary: The disturbance of hepatic lipid metabolism is closely associated with non-alcoholic fatty liver disease (NAFLD) and diabetes. This study examined the role of Mof, an acetyltransferase involved in obesity and carbon metabolism, in hepatic lipid metabolism. The results showed that Mof expression was altered in obese mice and NAFLD human liver, and the genes regulated by Mof were closely related to lipid metabolism. Inhibition of Mof led to increased lipid accumulation in normal mice or hepatic cells, while it improved lipid metabolism in diet-induced obesity mice or hepatic cells treated with palmitic acid. The study suggests that inhibition of Mof may be a potential therapeutic target for hepatic lipid metabolism disturbances.
Article
Oncology
Yan Zi Au, Muxin Gu, Etienne De Braekeleer, Malgorzata Gozdecka, Demetrios Aspris, Yusuke Tarumoto, Jonathan Cooper, Jason Yu, Swee Hoe Ong, Xi Chen, Konstantinos Tzelepis, Brian J. P. Huntly, George Vassiliou, Kosuke Yusa
Summary: The study identifies the importance of KAT7 in AML, showing that its loss leads to the loss of related marks and affects proliferation and differentiation of AML cells. The acetyltransferase activity of KAT7 is crucial for cell proliferation, making it a potential therapeutic target for this subtype of AML with poor prognosis.
Article
Cell Biology
Elsa Franco-Echevarria, Mathias Nielsen, Anna Schulten, Jitender Cheema, Tomos E. Morgan, Mariann Bienz, Caroline Dean
Summary: Polycomb repressive complex 2 (PRC2) mediates epigenetic silencing of target genes in animals and plants. In Arabidopsis, PRC2 relies on VEL accessory factors, including VRN5 and VIN3, to silence the FLC floral repressor locus under cold conditions. Our study reveals the distinct roles of VEL proteins in this process.
GENES & DEVELOPMENT
(2023)
Article
Plant Sciences
Zehao Zhang, Huijuan Qian, Zhongshi Wang, Ying Pang, Xiaowei Guan, Ansgar Poetsch, Dongmei Wang
Summary: Histone acetylation is an important epigenetic mechanism that plays a role in the regulation of various genes controlling growth, development, and response to environmental stresses in eukaryotes. However, the association of histone acetylation with dehydration stress and the genes involved in histone acetylation and deacetylation in red algae remain largely unknown. In this study, in silico analysis identified several histone acetyltransferase (HAT) and histone deacetylase (HDAC) genes in the red seaweed Pyropia yezoensis. The expression of these genes was found to be upregulated during dehydration, suggesting their potential roles in modulating gene expression under stress conditions. Experimental inhibition of HAT and HDAC activities confirmed their involvement in dehydration adaptation. This study provides insights into the regulation and function of HAT/HDAC during stress adaptation in red algae.
FRONTIERS IN PLANT SCIENCE
(2023)
Review
Pharmacology & Pharmacy
Hafiz Akbar Ali, Yalan Li, Akram Hafiz Muhammad Bilal, Tingting Qin, Ziqiao Yuan, Wen Zhao
Summary: The article discusses the role of bromodomain and extraterminal (BET) proteins in gene regulation and various pathological conditions. Research indicates that BET proteins are associated with several diseases, including cancer and inflammation. BET inhibitors have been developed to target these pathological conditions.
FRONTIERS IN PHARMACOLOGY
(2022)
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
Biotechnology & Applied Microbiology
Eui-Hwan Choi, Seobin Yoon, Young Eun Koh, Tae Kyung Hong, Jeong Tae Do, Bum-Kyu Lee, Yoonsoo Hahn, Keun P. Kim
Summary: The study reveals the functional roles of meiosis-specific cohesin complexes in mitotic chromosomes and their impact on chromosomal organization and the mitotic program in embryonic stem cells. The delicate balance between mitotic and meiotic cohesins is crucial for maintaining proper chromosome structure and function in ESCs.
Article
Neurosciences
Na Sun, Lina Yu, Yibo Gao, Longfei Ma, Jinxuan Ren, Ying Liu, Dave Schwinn Gao, Chen Xie, Ying Wu, Lieju Wang, Juncong Hong, Min Yan
Summary: The study reveals that nerve injury induced hypermethylation of the Oprm1 gene promoter and increased expression of MeCP2 in the injured DRG, leading to downregulation of MOR. Upregulated MeCP2 promotes binding of HDAC1 to hypermethylated regions of the Oprm1 gene promoter, reducing acetylation levels and inhibiting Oprm1 transcription, hence attenuating the analgesic effect of opioids. Targeting MeCP2/HDAC1 may offer a new solution for enhancing the therapeutic effect of opioids in clinical settings.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Harmony R. Salzler, Vasudha Vandadi, Benjamin D. McMichael, John C. Brown, Sally A. Boerma, Mary P. Leatham-Jensen, Kirsten M. Adams, Michael P. Meers, Jeremy M. Simon, Robert J. Duronio, Daniel J. McKay, A. Gregory Matera
Summary: Polycomb complexes regulate cell type-specific gene expression programs through heritable silencing. H3K27me3 is essential for this process, while disruption of H3K36 interferes with H3K27me3. Mutants of Drosophila replication-dependent or replication-independent histone H3 genes maintain Polycomb silencing and reach later stages of development, but combined mutants display widespread Hox gene misexpression and fail to develop past the first larval stage. Chromatin profiling revealed that the H3.2K36R mutation disrupts H3K27me3 levels broadly, while H3.3K36R animals are mostly unaffected. Analysis of H3.3 distributions showed the enrichment of H3.3 at presumptive Polycomb response elements located outside of silenced domains.
Review
Microbiology
Yiling Lai, Lili Wang, Weilu Zheng, Sibao Wang
Summary: Fungal pathogens use transcriptional reprogramming to regulate gene expression in response to changing host environments and defenses. Histone post-translational modifications play a crucial role in this process and are involved in fungal development, pathogenicity, and interactions with hosts.
Article
Cardiac & Cardiovascular Systems
Raja Chakraborty, Allison C. Ostriker, Yi Xie, Jui M. Dave, Ana Gamez-Mendez, Payel Chatterjee, Yaw Abu, Jake Valentine, Kimberly Lezon-Geyda, Daniel M. Greif, Vincent P. Schulz, Patrick G. Gallagher, William C. Sessa, John Hwa, Kathleen A. Martin
Summary: This study reveals that p300 and CBP play distinct and opposing roles in VSMC phenotypic switching and co-regulate chromatin modifications through different functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.
Article
Biochemistry & Molecular Biology
George Hunt, Ann Boija, Mattias Mannervik
Summary: Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb-group (PcG)-mediated transcriptional repression. This study reveals the association between the p300/CREB-binding protein (CBP) co-activator and PcG regions in Drosophila and mouse cells. CBP stabilizes Pol II at PcG-bound repressive sites and promotes Pol II pausing, which are necessary for R-loop formation and nucleosome depletion at Polycomb Response Elements (PREs), thereby supporting PcG-mediated silencing.
Article
Plant Sciences
Laura Poza-Viejo, Miriam Paya-Milans, Patxi San Martin-Uriz, Laura Castro-Labrador, David Lara-Astiaso, Mark D. Wilkinson, Manuel Pineiro, Jose A. Jarillo, Pedro Crevillen
Summary: Epigenetic regulation is crucial for optimal development and maintenance of gene expression profiles. This study uncovers the epigenetic mechanisms involved in flowering time regulation in Brassica rapa, shedding light on the conserved and distinct regulatory mechanisms between model and crop species.
PLANT CELL AND ENVIRONMENT
(2022)
Article
Cell Biology
Wenjun Zhou, Zheng-Wen Nie, Dong-Jie Zhou, Xiang-Shun Cui
Summary: ACSS1/2 plays a critical role in maintaining ATP and histone acetylation levels in porcine early embryos during zygotic genome activation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Parasitology
Ana Paula Menezes, Ana Milena Murillo, Camila Gachet de Castro, Natalia Karla Bellini, Luiz Ricardo Orsini Tosi, Otavio Henrique Thiemann, Maria Carolina Elias, Ariel Mariano Silber, Julia Pinheiro Chagas da Cunha
Summary: Epigenetic marks are chemical modifications on chromatin-associated proteins and nucleic acids that affect gene expression. The connection between metabolism and epigenetics has been increasingly discovered, revealing how the environment influences gene regulation and phenotype diversity. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites causing human and livestock diseases.
TRENDS IN PARASITOLOGY
(2023)
Article
Microbiology
Joana Faria, Vanessa Luzak, Laura S. M. Muller, Benedikt G. Brink, Sebastian Hutchinson, Lucy Glover, David Horn, T. Nicolai Siegel
Summary: The study reveals a mechanism in Trypanosoma brucei where a single expressed antigen-coding gene interacts with a major messenger RNA splicing locus in a specific nuclear compartment, ensuring monogenic expression. Specific proteins VEX1 and VEX2 are associated with an antigen exclusion complex, playing a role in this process of antigen transcription and mRNA splicing. Depletion of VEX2 results in loss of monogenic antigen expression and increased interactions between previously silent antigen genes and the splicing locus.
NATURE MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carys Davies, Cher-Pheng Ooi, Georgios Sioutas, Belinda S. Hall, Haneesh Sidhu, Falk Butter, Sam Alsford, Bill Wickstead, Gloria Rudenko
Summary: The African trypanosome Trypanosoma brucei relies on a protective VSG coat for survival in mammalian hosts. A whole genome RNAi library screen identified a novel DNA binding protein TbSAP, which plays an important role in silencing the extensive VSG repertoire in bloodstream form T. brucei.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Parasitology
David Horn
Summary: Genome-scale genetic screens have played a crucial role in African trypanosomes by uncovering mechanisms related to drug resistance, metabolism, and gene expression control. They have also been effective in identifying potential antitrypanosomal drug targets.
TRENDS IN PARASITOLOGY
(2022)
Article
Microbiology
Juliana Nunes Roson, Marcela de Oliveira Vitarelli, Hellida Marina Costa-Silva, Kamille Schmitt Pereira, David da Silva Pires, Leticia de Sousa Lopes, Barbara Cordeiro, Amelie Kraus, Karin Navarro Tozzi Cruz, Simone Guedes Calderano, Stenio Perdigao Fragoso, T. Nicolai Siegel, Maria Carolina Elias, Julia Pinheiro Chagas da Cunha
Summary: This study focused on the unique features of gene expression regulation in trypanosomatids. Through histone ChIP-seq analysis, it was found that H2B.V was enriched at critical genomic regions in T. cruzi and interacted with chromatin acetylation factors. Parasites with reduced H2B.V levels showed higher rates of differentiation and infectivity.
Article
Multidisciplinary Sciences
Yanika Borg, Sam Alsford, Vasos Pavlika, Alexei Zaikin, Darren N. Nesbeth
Summary: Kinetoplastid protozoa, with unique properties, have been shown to hold bioengineering potential. This study successfully constructed an oscillatory gene network in Trypanosoma brucei for the first time, laying the foundation for future synthetic biology research.
Article
Biochemistry & Molecular Biology
Simone Altmann, Eva Rico, Sandra Carvalho, Melanie Ridgway, Anna Trenaman, Hannah Donnelly, Michele Tinti, Susan Wyllie, David Horn
Summary: This study reports a simple method for rapid and precise editing of priority drug targets in trypanosomatids. By targeting and editing drug targets, combined with sequencing technology, potential impacts on drug efficacy can be assessed quickly.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Gustavo Bravo Ruiz, Michele Tinti, Melanie Ridgway, David Horn
Summary: VSG expression plays a crucial role in parasite virulence and is a fascinating subject in extreme biology. This study identified three candidate VSG regulators and demonstrated the role of CFB2 in controlling VSG expression through the VSG 3' UTR. Additionally, insights into the connections between VSG expression control, ribosomal protein expression, and cytokinesis were revealed.
Correction
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
NATURE REVIEWS MICROBIOLOGY
(2022)
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are major causes of death and illness, particularly in low- and middle-income countries. The development of new medicines for leishmaniasis and Chagas disease is urgently needed, with limited progress in the clinical pipeline for Chagas disease. This review provides an overview of recent advances in understanding the biology of these pathogens, with a focus on drug discovery, as well as the development of new drug candidates and potential solutions to overcome challenges in clinical development.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Catarina A. Marques, Melanie Ridgway, Michele Tinti, Andrew Cassidy, David Horn
Summary: In this study, a genome-wide RNA-interference library screen was used to investigate the cell cycle defects in Trypanosoma brucei. The results provide comprehensive functional genomic evidence for the known and novel machineries, pathways, and regulators that coordinate trypanosome cell cycle progression.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Livio Racane, Lucija Pticek, Sanja Kostrun, Silvana Raic-Malic, Martin Craig Taylor, Michael Delves, Sam Alsford, Francisco Olmo, Amanda Fortes Francisco, John M. Kelly
Summary: We designed and synthesized a series of symmetric benzothiazole derivatives and evaluated their efficacy against Trypanosoma brucei and Plasmodium falciparum. One compound showed high selectivity and trypanocidal activity, curing mice infected with trypanosomiasis. It also exhibited activity against the malaria parasite.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Douglas Escrivani, Viktor Scheidt, Michele Tinti, Joana Faria, David Horn
Summary: Some pathogens use antigenic variation to evade mammalian host adaptive immune responses. African trypanosomes employ variant surface glycoproteins (VSGs) to continually switch their active VSGs and avoid immune recognition. Switched trypanosomes compete in a predictable manner that is dependent on the activated VSG, and the population of cells that activates minichromosome derived VSGs has a competitive advantage.
Article
Microbiology
Anna Trenaman, Michele Tinti, Abdelmadjid Atrih, David Horn
Summary: Nucleoside analogs are widely used as anti-infective agents, but their potential as anti-parasitic agents has not been fully explored. This study identified two proteins, Tb927.6.2800 and HD82, associated with purine analog resistance in African trypanosomes. The findings also validated two nucleoside kinases involved in pro-drug activation. HD82, related to the mammalian nuclear viral restriction factor SAMHD1, sensitized trypanosomes to nucleoside analogs by reducing native nucleotide pools. This study provides insights into nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are causing significant death and morbidity, especially in low- and middle-income countries. There is a critical need for new medications for leishmaniasis and Chagas disease, while the clinical development pipeline for Chagas disease remains sparse. This review discusses recent advancements in understanding the biology of these pathogens, with a focus on drug discovery, and explores progress in developing new drug candidates and identifying potential molecular targets. The challenges in developing new clinical candidates are also discussed, along with potential solutions to overcome these hurdles.
NATURE REVIEWS MICROBIOLOGY
(2023)