Article
Genetics & Heredity
Phoebe Y. T. Lu, Alyssa C. Kirlin, Maria J. Aristizabal, Hilary T. Brewis, Nancy Levesque, Dheva T. Setiaputra, Nikita Avvakumov, Joris J. Benschop, Marian Groot Koerkamp, Frank C. P. Holstege, Nevan J. Krogan, Calvin K. Yip, Jacques Cote, Michael S. Kobor
Summary: The NuA4 lysine acetyltransferase complex can function as picNuA4 independently, and its regulation involves physical interactions between the C-terminus of Epl1 and the HSA domain of Eaf1. Disruption of the Epl1-Eaf1 interaction can release picNuA4 from NuA4, indicating a complex relationship between the two in regulating picNuA4 amount and activity.
Article
Cell Biology
Jibo Zhang, Aakanksha Gundu, Brian D. Strahl
Summary: In this study, Zhang et al. investigate how transcription programs rapidly adjust to changing metabolic and cellular cues, with a focus on the role of the Yaf9 component in maintaining timely transcription of metabolic genes across the yeast metabolic cycle. They find that Yaf9 recruits chromatin regulatory complexes to deposit H2A.Z and acetylate H4, promoting transcriptional initiation during the oxidative phase. These findings suggest a dynamic chromatin and transcription initiation factor signature is necessary for proper regulation of metabolic gene transcription during the yeast metabolic cycle, with unique regulatory mechanisms at distinct metabolic states.
GENES & DEVELOPMENT
(2021)
Article
Biology
Stefan A. Zukin, Matthew R. Marunde, Irina K. Popova, Katarzyna M. Soczek, Eva Nogales, Avinash B. Patel
Summary: The structure of the central hub of the NuA4 protein complex, which connects the histone acetyltransferase (HAT) and Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (TINTIN) modules, has been determined. The HAT module recognizes nucleosomes with hyperacetylated H3 tails, while the TINTIN module recognizes nucleosomes with hyperacetylated H2A and H4 tails. This study provides insights into how NuA4 is recruited to specific genomic sites.
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)
Review
Biochemistry & Molecular Biology
Qiong Wu, Anders E. Berglund, Arnold B. Etame
Summary: Glioblastoma is highly resistant to standard therapies and the durability of response to the best chemotherapy agent, Temozolomide, is often short-lived due to tumor resistance. The need for therapies that can provide synergy to chemoradiation is urgent, as adaptive resistance evolution in GBM is facilitated through treatment-induced epigenetic modifications. Understanding and targeting these epigenetic modifications associated with GBM resistance is a top priority.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Francisco Gimeno-Valiente, Gerardo Lopez-Rodas, Josefa Castillo, Luis Franco
Summary: This review focuses on the interconnections between epigenetics and alternative splicing in the development of cancer. It discusses the mechanisms involved in these interconnections and the potential diagnostic and therapeutic tools that can be derived from them. The reversible nature of epigenetic alterations and the possibility of correcting aberrant alternative splicing offer promising therapeutic possibilities for cancer treatment.
Article
Parasitology
Samantha J. Emery-Corbin, Joshua J. Hamey, Balu Balan, Laura Rojas-Lopez, Staffan G. Svard, Aaron R. Jex
Summary: This study provides the first known molecular map of histone post-translational modifications in Giardia, identifying over 50 previously unreported histone modifications. The research suggests conserved histone modifications in Giardia, equivalent to many other eukaryotes, and indicates the presence of similar epigenetic mechanisms in the parasite. The study is a substantial step towards understanding the associations of histone modifications in parasite development and virulence.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Multidisciplinary Sciences
Keke Qu, Kangjing Chen, Hao Wang, Xueming Li, Zhucheng Chen
Summary: This study reports the cryo-electron microscopy structure of NuA4 bound to the nucleosome, shedding light on the assembly of NuA4 and its role in nucleosome recognition and transcription co-activation.
Article
Multidisciplinary Sciences
Albert Serra-Cardona, Shoufu Duan, Chuanhe Yu, Zhiguo Zhang
Summary: The study demonstrates that mutations in replicative helicase subunit, Mcm2, and leading strand DNA polymerase subunit, Dpb3, lead to asymmetric distribution of H3K4me3 during DNA replication, and the H3K4 methyltransferase complex, COMPASS, plays a role in restoring a more symmetric distribution of H3K4me3 at replicating DNA strands during cell cycle progression.
Article
Cell Biology
Suhila Sawesi, Sridhar A. Malkaram, Zakaria Y. Abd Elmageed, Tamer E. Fandy
Summary: This study compared the effects of curcumin and dimethoxycurcumin (DMC) on histone posttranslational modifications and enzymatic activity. It was found that both drugs had similar effects on the activity of histone lysine methyltransferase (HKMTs) and histone lysine demethylase (HKDMs) enzymes. However, the changes in histone modifications induced by the two drugs were different. These findings support the use and development of curcumin and DMC as epigenetic modifiers in cancer treatment.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Werner Giehl Glanzner, Mariana Priotto de Macedo, Karina Gutierrez, Vilceu Bordignon
Summary: Animal cloning has been successful in over 20 mammalian species using SCNT, with pigs being the leading species. The importance of pig cloning lies in its relevance to food production and biomedical applications. Despite recognized progress, the overall efficiency of SCNT in pigs remains low. New strategies for chromatin and epigenetic reprogramming may revolutionize pig cloning.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Elizabeth A. Pollina, Daniel T. Gilliam, Andrew T. Landau, Cindy Lin, Naomi Pajarillo, Christopher P. Davis, David A. Harmin, Ee-Lynn Yap, Ian R. Vogel, Eric C. Griffith, M. Aurel Nagy, Emi Ling, Erin E. Duffy, Bernardo L. Sabatini, Charles J. Weitz, Michael E. Greenberg
Summary: Neuronal activity poses a risk to genome stability, but neurons have a specialized DNA repair mechanism that protects against damage caused by activity. This mechanism involves a specific complex called NPAS4-NuA4, which repairs DNA double-strand breaks and protects regulatory elements from somatic mutations. Disruption of this complex can lead to neurodevelopmental disorders, neurodegeneration, and reduced lifespan.
Article
Multidisciplinary Sciences
Rodrigo Fraile, Laura Sanchez-Mir, Guillem Murciano-Julia, Jose Ayte, Elena Hidalgo
Summary: Through studying different phosphomutants of Atf1, we found that phosphorylation plays an important role in heterochromatin establishment and silencing at the mat locus. Unphosphorylated Atf1 can recruit repressive complexes and participate in heterochromatin assembly.
Review
Biochemistry & Molecular Biology
Lee-Ann Niekerk, Mogamat Fahiem Carelse, Olalekan Olanrewaju Bakare, Vuyo Mavumengwana, Marshall Keyster, Arun Gokul
Summary: The review discusses the negative impact of heavy metals such as cadmium on staple crop production and the role of epigenetic mechanisms in enhancing cadmium tolerance. Understanding and utilizing these genetic mechanisms can provide a crucial framework for improving plant cadmium tolerance in future studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Biochemistry & Molecular Biology
Yogita Jethmalani, Erin M. Green
CURRENT PROTEIN & PEPTIDE SCIENCE
(2020)
Article
Oncology
Zhentian Wang, Simone Hausmann, Ruitu Lyu, Tie-Mei Li, Shane M. Lofgren, Natasha M. Flores, Mary E. Fuentes, Marcello Caporicci, Ze Yang, Matthew Joseph Meiners, Marcus Adrian Cheek, Sarah Ann Howard, Lichao Zhang, Joshua Eric Elias, Michael P. Kim, Anirban Maitra, Huamin Wang, Michael Cory Bassik, Michael-Christopher Keogh, Julien Sage, Or Gozani, Pawel K. Mazur
Article
Genetics & Heredity
Kadir C. Akdemir, Victoria T. Le, Justin M. Kim, Sarah Killcoyne, Devin A. King, Ya-Ping Lin, Yanyan Tian, Akira Inoue, Samirkumar B. Amin, Frederick S. Robinson, Manjunath Nimmakayalu, Rafael E. Herrera, Erica J. Lynn, Kin Chan, Sahil Seth, Leszek J. Klimczak, Moritz Gerstung, Dmitry A. Gordenin, John O'Brien, Lei Li, Yonathan Lissanu Deribe, Roel G. Verhaak, Peter J. Campbell, Rebecca Fitzgerald, Ashby J. Morrison, Jesse R. Dixon, P. Andrew Futreal
Review
Biotechnology & Applied Microbiology
Kamakoti P. Bhat, H. Umit Kaniskan, Jian Jin, Or Gozani
Summary: Protein lysine methylation is a crucial post-translational modification that plays a role in various diseases. Drugs targeting specific KMTs have been developed, with some already approved for clinical use and others under evaluation. These KMTs are emerging as promising new targets for drug development to treat diverse diseases.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Gang Yuan, Natasha M. Flores, Simone Hausmann, Shane M. Lofgren, Vladlena Kharchenko, Maria Angulo-Ibanez, Deepanwita Sengupta, Xiaoyin Lu, Iwona Czaban, Dulat Azhibek, Silvestre Vicent, Wolfgang Fischle, Mariusz Jaremko, Bingliang Fang, Ignacio I. Wistuba, Katrin F. Chua, Jack A. Roth, John D. Minna, Ning-Yi Shao, Lukasz Jaremko, Pawel K. Mazur, Or Gozani
Summary: Amplification of the chromosomal region 8p11-12 is common in lung squamous cell carcinoma (LUSC) and the NSD3 gene in this region is identified as a key regulator of LUSC tumorigenesis. NSD3 depletion attenuates tumor growth and enhances survival in LUSC, suggesting its potential as a therapeutic target. Additionally, NSD3-dependent LUSC xenografts are sensitive to bromodomain inhibition, indicating a vulnerability of LUSC to this treatment.
Article
Cardiac & Cardiovascular Systems
Siyeon Rhee, David T. Paik, Johnson Y. Yang, Danielle Nagelberg, Ian Williams, Lei Tian, Robert Roth, Mark Chandy, Jiyeon Ban, Nadjet Belbachir, Seokho Kim, Hao Zhang, Ragini Phansalkar, Ka Man Wong, Devin A. King, Caroline Valdez, Virginia D. Winn, Ashby J. Morrison, Joseph C. Wu, Kristy Red-Horse
Summary: The study identified pathological endocardial cell population and dysregulated angiocrine factors in non-compaction cardiomyopathy, which significantly affected cardiomyocyte behavior. The deletion of chromatin remodeller gene Ino80 inhibited cardiomyocyte proliferation and promoted maturation, suggesting a model where coronary endothelial cells promote myocardial compaction through secreted factors.
EUROPEAN HEART JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Ashby J. Morrison
Summary: Cellular adaptation to nutrient environment is crucial for survival, failure to adapt can result in cell death and diseases. Metabolism alterations, particularly in cancer cells, play a significant role in the pathogenesis of diseases. Recent studies have shown the interplay between metabolic pathways, epigenetic modifications, and transcriptional regulation in cancer cells.
Article
Biotechnology & Applied Microbiology
Brian S. Perez, Ka Man Wong, Erin K. Schwartz, Rafael E. Herrera, Devin A. King, Pablo E. Garcia-Nieto, Ashby J. Morrison
Summary: This study found a high degree of similarity between UV-induced 6-4PP and CPD formation, both enriched in heterochromatin regions. However, bivalent and Polycomb-repressed chromatin states were uniquely more susceptible to 6-4PPs. Disparate patterns were observed when comparing UV susceptibility, repair, and melanoma mutation frequency, indicating complex associations in these regions. Functional enrichment analysis hinted at negative selection mechanisms in regions essential for cell viability, immune function, and inducing cell death when mutated.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2021)
Article
Biology
Yogita Jethmalani, Khoa Tran, Maraki Y. Negesse, Winny Sun, Mark Ramos, Deepika Jaiswal, Meagan Jezek, Shandon Amos, Eric Joshua Garcia, DoHwan Park, Erin M. Green
Summary: Set4 is a member of the Set3 subfamily of SET domain proteins, regulating gene expression and maintaining gene repressive mechanisms within yeast subtelomeres, crucial under hypoxic conditions.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biology
Ka Man Wong, Devin A. King, Erin K. Schwartz, Rafael E. Herrera, Ashby J. Morrison
Summary: Carcinogen susceptibility, regulated by RB1 tumor suppressor, plays an important role in cancer mutagenesis. Deletion of RB1 increases UV lesion susceptibility in centromere and telomere-proximal regions, leading to accelerated mutagenic potential in cancers.
LIFE SCIENCE ALLIANCE
(2022)
Article
Multidisciplinary Sciences
Christine E. Peters, Ursula Schulze-Gahmen, Manon Eckhardt, Gwendolyn M. Jang, Jiewei Xu, Ernst H. Pulido, Melanie Ott, Or Gozani, Kliment A. Verba, Ruth Huettenhain, Jan E. Carette, Nevan J. Krogan
Summary: This study reports the structure of the interaction between Actin histidine methyltransferase SETD3 and the enterovirus CV-B3 2A protease, revealing the importance of the SET domain for virus replication. Mutations in key residues of the SET domain result in reduced binding to 2A and complete protection against enteroviral infection.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Chen Chen, June Ho Shin, Zhuoqing Fang, Kevin Brennan, Nina B. Horowitz, Kathleen L. Pfaff, Emma L. Welsh, Scott J. Rodig, Olivier Gevaert, Or Gozani, Ravindra Uppaluri, John B. Sunwoo
Summary: In head and neck squamous cell carcinoma (HNSCC), inactivating mutations in the histone methyltransferase NSD1 disproportionately contribute to tumor development and immune exclusion. Understanding the NSD1-mediated mechanism and targeting the histone-modifying enzyme KDM2A could enhance T-cell infiltration and suppress tumor growth in HNSCC.
Article
Biochemistry & Molecular Biology
Ricardo Mack, Or Gozani
Summary: The use of CRISPR technology and a high-content functional genomics screening platform sheds light on chromatin regulation and reveals a potential strategy for treating an aggressive type of leukemia.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Meagan Jezek, Winny Sun, Maraki Y. Negesse, Zachary M. Smith, Alexander Orosz, Erin M. Green
Summary: Set1 is an H3K4 methyltransferase involved in various genomic functions. It plays a role in subtelomeric gene repression through its catalytic activity towards H3K4 and regulates telomere length through its catalytic activity but likely independent of the H3K4 substrate. Set1 also calibrates the abundance of critical telomere maintenance proteins through transcriptional and posttranscriptional pathways. These findings provide new insights into the roles of Set1 in telomere maintenance and have implications for Set1-related methyltransferases in other systems.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Biochemical Research Methods
Deepika Jaiswal, Rashi Turniansky, Erin M. Green
Summary: Protein regulation by post-translational modifications and protein-protein interactions is critical, and an immunoaffinity purification approach can be applied to identify post-translational modifications or protein binding partners.
