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
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
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
Genetics & Heredity
Salar Ahmad, Valerie Cote, Xue Chengid, Gaelle Bourriquen, Vasileia Sapountzi, Mohammed Altafid, Jacques Cote
Summary: The NuA4 histone acetyltransferase complex plays a crucial role in DNA double-strand break repair, favoring homologous recombination during the S/G2 phase of the cell cycle. It exhibits an antagonistic relationship with non-homologous end joining (NHEJ) factors, potentially participating in the single-strand annealing (SSA) repair pathway in G1 and regulating DNA end resection. This suggests a reciprocal regulatory function of NuA4 and NHEJ factors in repair pathway choice and alternative repair mechanisms, particularly in situations where DNA end resection occurs in G1.
Article
Genetics & Heredity
Xue Cheng, Valerie Cote, Jacques Cote
Summary: In this study, the authors found that the enzymes NuA4 and SAGA play essential roles in DNA double-strand break repair, with their cooperation facilitating nucleosome reassembly and DNA end recombination processes. Their collaboration is crucial for recruiting chromatin remodelers, targeted acetylation of repair factors, and homologous recombination, demonstrating a multifaceted and conserved cooperation mechanism between acetyltransferase complexes for efficient repair of DNA breaks.
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
Cell Biology
Amel Mameri, Jacques Cote
Summary: The multisubunit NuA4/TIP60 complex is involved in various biological processes as a lysine acetyltransferase, chromatin modifying factor and gene co-activator. However, understanding of its molecular mechanisms is limited and contradictory, thus requiring further investigation. Recently, the identification of JAZF1 as a novel subunit linked to metabolic homeostasis has provided an exciting direction for exploring the role of NuA4/TIP60 in metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jie Li, Phillip M. Galbo, Weida Gong, Aaron J. Storey, Yi-Hsuan Tsai, Xufen Yu, Jeong Hyun Ahn, Yiran Guo, Samuel G. Mackintosh, Ricky D. Edmondson, Stephanie D. Byrum, Jason E. Farrar, Shenghui He, Ling Cai, Jian Jin, Alan J. Tackett, Deyou Zheng, Gang Greg Wang
Summary: This study reveals that the fusion gene ZMYND11-MBTD1 (ZM) induces AML in a subset of patients by activating the NuA4/TIP60 histone acetyltransferase complex. ZM directly regulates the expression of pro-leukemic genes, promoting the development of AML through sustaining an active chromatin state.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Qiaoyun Zheng, Hongfang Qiu, Hongen Zhang, Alan G. Hinnebusch
Summary: The study found that NuA4, like Gcn5, is an important HAT complex that acts additively in evicting and repositioning promoter nucleosomes and stimulating transcription of starvation-induced genes. However, NuA4 is generally more important than Gcn5 in promoter nucleosome eviction, TBP recruitment, and transcription at most other genes. SAGA and NuA4 exhibit an intricate interplay in nucleosome eviction, PIC assembly, and transcription, which differs between the starvation-induced and basal transcriptomes.
NUCLEIC ACIDS RESEARCH
(2023)
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
Cell Biology
Deepthi Sudarshan, Nikita Avvakumov, Marie-Eve Lalonde, Nader Alerasool, Charles Joly-Beauparlant, Karine Jacquet, Amel Mameri, Jean-Philippe Lambert, Justine Rousseau, Catherine Lachance, Eric Paquet, Lara Herrmann, Samarth Thonta Setty, Jeremy Loehr, Marcus Q. Bernardini, Marjan Rouzbahman, Anne-Claude Gingras, Benoit Coulombe, Arnaud Droit, Mikko Taipale, Yannick Doyon, Jacques Cote
Summary: Chromosomal translocations in endometrial stromal sarcomas and ossifying fibromyxoid tumors lead to fusion of NuA4/TIP60 and PRC2 complexes, resulting in mislocalization of histone marks and aberrant gene expression.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Yoo Jin Joo, Stephen Buratowski
Summary: In this study, an uncharacterized protein Gds1 was found to interact with the RNA polymerase II transcription initiation complex and modulate its function in specific promoter contexts. Additionally, Gds1 was found to be associated with the histone H4 acetyltransferase NuA4 and deletion of GDS1 led to reduced H4 acetylation and phenotypic changes.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yahli Lorch, Roger D. Kornberg, Barbara Maier-Davis
Summary: The high positive charge of histone tails, which is concentrated in the N- and C-terminal tails, was previously believed to contribute to the stability of nucleosomes. However, we have found that the positive charge actually contributes to instability and plays a crucial role in chromatin remodeling. We have shown that the tails are necessary for histone octamer removal by the RSC chromatin remodeling complex and for histone octamer transfer from nucleosomes to DNA, and this activity is directly related to their positive charge.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Anahita Lashgari, Pata-Eting Kougnassoukou Tchara, Jean-Philippe Lambert, Jacques Cote
Summary: In eukaryotic cells, DNA double-strand breaks can be repaired through nonhomologous end-joining or homologous recombination. The choice of repair pathway is regulated by antagonistic relationship between repair factors specific to each pathway and is dependent on the cell cycle. The molecular mechanisms of this decision involve post-translational modifications of chromatin surrounding the break. Recent advances have focused on the function of the NuA4/TIP60 histone acetyltransferase/chromatin remodeling complex in DSBs repair, particularly its collaboration with the SAGA acetyltransferase complex and their role in regulating chromatin dynamics, DNA end resection, and recombination.
Article
Multidisciplinary Sciences
Na Jiang, Binna Lv, Haixia Wu, Shidong Li, Manhong Sun
Summary: The study constructed a TMT-labelled lysine acetylome in Clonostachys chloroleuca 67-1, identifying a large number of Kac proteins with differential modification. Bioinformatics analysis showed that these Kac proteins are involved in diverse functions and have a broad regulatory effect.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ana Lilia Torres-Machorro, Lauren G. Clark, Christie S. Chang, Lorraine Pillus
MOLECULAR AND CELLULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Ana Lilia Torres-Machorro, John P. Aris, Lorraine Pillus
NUCLEIC ACIDS RESEARCH
(2015)
Article
Genetics & Heredity
Naomi E. Searle, Ana Lilia Torres-Machorro, Lorraine Pillus
Article
Multidisciplinary Sciences
Esther Magdalena Marquez-Lona, Ana Lilia Torres-Machorro, Frankie R. Gonzales, Lorraine Pillus, Gentry N. Patrick
Article
Genetics & Heredity
Ana Lilia Torres-Machorro, Roberto Hernandez, John F. Alderete, Imelda Lopez-Villasenor
Article
Genetics & Heredity
Ana Lilia Torres-Machorro, Lorraine Pillus
Article
Biochemistry & Molecular Biology
Miguel Ramirez-Aragon, Fernando Hernandez-Sanchez, Tatiana S. Rodriguez-Reyna, Ivette Buendia-Roldan, Gael Guitron-Castillo, Carlos A. Nunez-Alvarez, Diego F. Hernandez-Ramirez, Sergio A. Benavides-Suarez, Alexia Esquinca-Gonzalez, Ana Lilia Torres-Machorro, Criselda Mendoza-Milla
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Environmental Sciences
Carlos Ramos, Rebeca Canedo-Mondragon, Carina Becerril, Georgina Gonzalez-Avila, Ana Laura Esquivel, Ana Lilia Torres-Machorro, Martha Montano
Summary: Exposure to short-term wood smoke was found to significantly increase total cells, macrophages, neutrophils, and collagen in the respiratory system of guinea pigs, leading to overexpression of pro-inflammatory cytokines, MMPs, and TIMPs in lung tissue.
Review
Biochemistry & Molecular Biology
Ana Lilia Torres-Machorro
Summary: The bHLH transcription factor family plays essential roles in tissue development, cell differentiation, and disease, with positive, negative, and inactive transcriptional functions. Dimeric interactions among family members, such as E-protein homodimers and heterodimers with tissue-specific TFs or ID proteins, contribute to a complex transcriptional network defining cell fate. The central role of homodimers of tissue-specific bHLH TFs in the regulatory network, as well as the formation of transcriptionally inactive heterodimers, are highlighted. Detailed information on function, classification, and developmental roles of vertebrate bHLH TFs in four major classes is provided.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Naomi E. Searle, Lorraine Pillus
Article
Biochemistry & Molecular Biology
AL Torres-Machorro, R Hernández, J Sánchez, I López-Villaseñor
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2006)
Review
Microbiology
Ana Lilia Torres-Machorro, Roberto Hernandez, Ana Maria Cevallos, Imelda Lopez-Villasenor
FEMS MICROBIOLOGY REVIEWS
(2010)