Article
Cell Biology
Xin Li, Shanshan Wang, Xilan Yu, Shanshan Li
Summary: Autophagy is a catabolic process that maintains homeostasis and is involved in cell differentiation and development. The chromatin remodeling complex INO80 and histone variant H2A.Z have been identified as new regulators of autophagy, and the histone deacetylase Rpd3L complex plays a role in repressing autophagy by deacetylating Ino80 and H2A.Z. These findings highlight the importance of chromatin remodelers and histone variants in regulating autophagy in response to nutrient availability.
Review
Biochemistry & Molecular Biology
Ji-Yun Shang, Xin-Jian He
Summary: Adenosine triphosphate-dependent chromatin remodeling complexes play a crucial role in transcription, DNA replication, and genome stability regulation in eukaryotes. However, the study of chromatin remodeling complexes in plants lags behind yeast and animals. Recent research has identified and characterized the composition and function of chromatin remodeling enzymes in Arabidopsis, providing a foundation for further investigation into the molecular mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ieva Vaicekauskaite, Rasa Sabaliauskaite, Juozas Rimantas Lazutka, Sonata Jarmalaite
Summary: Ovarian cancer is the fifth leading cause of women's death from cancers, with high mortality rate due to late presence and lack of modern diagnostic tools. It is a highly heterogeneous disease, leading to early treatment failure. Exploring molecular mechanisms of ovarian cancer can enhance our understanding and provide new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Laura J. Hsieh, Muryam A. Gourdet, Camille M. Moore, Elise N. Munoz, Nathan Gamarra, Vijay Ramani, Geeta J. Narlikar
Summary: The INO80 chromatin remodeling complex plays a critical role in transcription by preferentially mobilizing hexasomes over nucleosomes. It does so by dislodging an H2A-H2B dimer, allowing nucleosomes to transiently resemble hexasomes. This versatile mechanism allows INO80 to regulate chromatin architecture during transcription, replication, and repair.
Article
Biochemistry & Molecular Biology
Junaid Ali Shah, Yujuan Miao, Jinmeng Chu, Wenqi Chen, Qingzhi Zhao, Chengyu Cai, Saadullah Khattak, Fei Wang, Jingji Jin
Summary: This study reveals that the INO80 chromatin remodeling complex transcriptionally controls the expression of miR-372 and there is a mutual regulatory mechanism between them. The mutual modulation affects cell proliferation and the p53/p21 signaling pathway, suggesting a synergistic anti-tumor role of the INO80 complex and miR372.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Kyle Brown, Pin Yu Chew, Steven Ingersoll, Jorge R. Espinosa, Anne Aguirre, Axel Espinoza, Joey Wen, Kalkidan Astatike, Tatiana G. Kutateladze, Rosana Collepardo-Guevara, Xiaojun Ren
Summary: This study reveals the assembly and regulation mechanism of Polycomb repressive complex 1 (PRC1). The findings demonstrate that the formation and dynamic properties of PRC1 condensates are sensitively regulated by their composition and stoichiometry.
Article
Biochemistry & Molecular Biology
Yasaman Zahedi, Shengyuan Zeng, Karl Ekwall
Summary: Cellular quiescence is a vital physiological state that occurs at the G(0) stage in both single-celled and multicellular eukaryotes. The chromatin remodeling complex Ino80C has been found to play a crucial role in the survival of quiescent cells. In this study, we demonstrate that Ino80C is involved in the regulation of gene expression in G(0) cells. Null mutants for certain Ino80C subunits, the histone variant H2A.Z, and Inositol kinase Asp1 exhibit similar phenotypes in quiescence, including reduced genome-wide transcription and failure to activate quiescence genes, particularly those localized to subtelomeric regions. Our findings suggest that Ino80C evicts H2A.Z from chromatin in quiescent cells, leading to the inactivation of subtelomeric boundary element and the activation of genes necessary for survival in quiescence.
CHROMOSOME RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Celine Duc, Christophe Thiriet
Summary: The review focuses on the remodeling of chromatin during DNA replication in the S-phase, including the eviction of nucleosomes and the assembly of newly synthesized histones. The recycling of parental histones and the nuclear import of histones are also discussed in relation to epigenetic inheritance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hai T. Dao, Linh T. D. Pham
Summary: Structural and biochemical studies have shown that the nucleosome acidic patch plays a crucial role in regulating the function of nuclear proteins. Different remodeler families interact with the acidic patch in distinct ways, leading to specific remodeling outcomes. The impact of cancer-related histone mutations on nucleosome remodeling is not well understood. Recent advancements in chromatin reconstitution have shed light on the effects of acidic patch mutations on chromatin structure.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Multidisciplinary Sciences
Sudarshan Pinglay, Dylan P. Rahe, Emily Huang, Ran Brosh, Nicholas E. Mamrak, Benjamin R. King, Sergei German, John A. Cadley, Lila Rieber, Nicole Easo, Timothee Lionnet, Shaun Mahony, Matthew T. Maurano, Liam J. Holt, Esteban O. Mazzoni, Jef D. Boeke
Summary: Precise Hox gene expression is essential for embryonic patterning. This study utilizes synthetic regulatory reconstitution to study gene regulation and focuses on the HoxA cluster. The researchers synthesized and delivered variant rat HoxA clusters to an ectopic location in the mouse genome, and found that a minimal HoxA cluster could reproduce the correct patterns of chromatin remodeling and transcription in response to patterning signals, while the addition of distal enhancers was necessary for full transcriptional output.
Review
Microbiology
Thomas Hollin, Zeinab Chahine, Karine G. Le Roch
Summary: This study provides an up-to-date overview of the regulation of gene expression and complex epigenetic mechanisms in Plasmodium falciparum, the human malaria parasite. It also explores the importance of chromatin architecture and remodeling systems in various biological processes.
ANNUAL REVIEW OF MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jonna Heldrich, Carolyn R. Milano, Tovah E. Markowitz, Sarah N. Ur, Luis A. Vale-Silva, Kevin D. Corbett, Andreas Hochwagen
Summary: Successful meiotic recombination requires conserved axis proteins, which distribute on chromosomes through two independent pathways: a cohesin-dependent pathway and a cohesin-independent pathway. These pathways result in a stereotypic distribution pattern and the formation of chromatin islands that influence chromosome structure.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Li Chen, Linna Tu, Gege Yang, David K. Banfield
Summary: Research has shown that GPI-anchored proteins undergo extensive remodeling before being transported to the plasma membrane, with remodeling of mannose 2 being crucial for cell viability. GPI-APs that have not undergone this remodeling can still reach the plasma membrane, but their presence triggers a unique stress response.
Article
Biochemistry & Molecular Biology
Lucia Falbo, Vincenzo Costanzo
Summary: Research has shown that in early embryonic development of certain metazoans, there is a transition in the number of replication origins to ensure accurate DNA replication. This novel form of epigenetic memory may impact various areas of vertebrate biology.
Review
Biochemistry & Molecular Biology
Shiv I. S. Grewal
Summary: Heterochromatin plays a crucial role in gene regulation, genome integrity, and silencing repetitive DNA elements. Histone modifications, specifically H3K9 methylation, are essential for the establishment and propagation of heterochromatin domains. Recent studies have highlighted the importance of modified histones, particularly H3K9me3, for epigenetic inheritance during cell division. This review discusses key experiments that have demonstrated the significance of modified histones in this process.
Article
Biochemistry & Molecular Biology
Christopher W. Akey, Digvijay Singh, Christna Ouch, Ignacia Echeverria, Ilona Nudelman, Joseph M. Varberg, Zulin Yu, Fei Fang, Yi Shi, Junjie Wang, Daniel Salzberg, Kangkang Song, Chen Xu, James C. Gumbart, Sergey Suslov, Jay Unruh, Sue L. Jaspersen, Brian T. Chait, Andrej Sali, Javier Fernandez-Martinez, Steven J. Ludtke, Elizabeth Villa, Michael P. Rout
Summary: This study provides a structure of the isolated yeast NPC and reveals how flexible connectors tie together different structural and functional layers. It also suggests an evolutionary and mechanistic link between assembly and transport. Additionally, the study identifies three major NPC variants that may signify functional specializations at the nuclear periphery.
Article
Biochemistry & Molecular Biology
Julian A. Harris, Bryan Faust, Arisbel B. Gondin, Marc Andre Damgen, Carl-Mikael Suomivuori, Nicholas A. Veldhuis, Yifan Cheng, Ron O. Dror, David M. Thal, Aashish Manglik
Summary: The neuropeptide substance P activates the neurokinin-1 receptor through interactions deep within the receptor, while interactions between the neuropeptide and the receptor extracellular loops regulate G protein signaling selectivity. This study sheds light on how different stimuli can lead to distinct G protein signaling at the same receptor.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Genetics & Heredity
Hannes Braberg, Ignacia Echeverria, Robyn M. Kaake, Andrej Sali, Nevan J. Krogan
Summary: Understanding the effects of genetic variation is a crucial problem in biology. Recent advancements in genetic datasets and deep learning approaches have enabled the modeling of protein structures and interactions, providing insights into the physical and functional consequences of sequence changes. Integrating structural data from different sources is also important for a comprehensive understanding of protein interactions.
NATURE REVIEWS GENETICS
(2022)
Editorial Material
Chemistry, Multidisciplinary
Yifan Cheng
Article
Biochemistry & Molecular Biology
Ignacia Echeverria, Hannes Braberg, Nevan J. Krogan, Andrej Sali
Summary: Integrative structure modeling is widely used for determining the architectures of biological assemblies, particularly those that are structurally heterogeneous. This study presents a method that converts in vivo genetic interaction measurements into spatial restraints for structural modeling. The approach is illustrated by determining the structure of the histone H3-H4 complex. The method is implemented in an open-source program, expanding the structural biology toolbox by enabling structural characterization based on in vivo data without the need for purification. The study compares genetic interaction measurements to other sources of structural information and suggests the use of new technologies, such as CRISPR-Cas9 gene editing, for determining genetic interactions.
Article
Multidisciplinary Sciences
Kaihua Zhang, Hao Wu, Nicholas Hoppe, Aashish Manglik, Yifan Cheng
Summary: In this study, Zhang et al. explore fusion protein strategies to facilitate cryo-EM structural studies of GPCRs alone, without signal transducers, in ligand-bound or unliganded form.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yen-Li Li, Caroline A. Langley, Caleigh M. Azumaya, Ignacia Echeverria, Nicholas M. Chesarino, Michael Emerman, Yifan Cheng, John D. Gross
Summary: The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. A3G protein of humans binds to HIV-1 Vif and inhibits its function by RNA-mediated mechanisms. This discovery sheds light on the molecular arms race between viruses and hosts.
Article
Biochemistry & Molecular Biology
Sun Kyung Kim, Miles Sasha Dickinson, Janet Finer-Moore, Ziqiang Guan, Robyn M. Kaake, Ignacia Echeverria, Jen Chen, Ernst H. Pulido, Andrej Sali, Nevan J. Krogan, Oren S. Rosenberg, Robert M. Stroud
Summary: We purified polyketide synthase 13 (Pks13) from mycobacteria and determined its structures using cryo-EM. This enzyme is involved in the synthesis of mycolic acids, which are essential for the cell wall of Mycobacterium tuberculosis. Our findings provide insights into the mechanism of these enzymes and have implications for drug development.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Arpit Gupta, Alfred M. Lentzsch, Alex Siegel, Zanlin Yu, Un Seng Chio, Yifan Cheng, Shu-ou Shan
Summary: Ring-forming AAA(+) chaperones like Skd3 act as both disaggregases and protein refolding enzymes, and their assembly states play a crucial role in determining their activities. High-resolution structures of Skd3 hexamers capture the ratchet-like motions that mediate substrate extraction, while further assembly into dodecameric cages allows solubilized substrate proteins to attain near-native states. Mutants defective in dodecamer assembly retain disaggregase activity but are impaired in client refolding, highlighting the importance of the hexameric and dodecameric states in Skd3's functions.
Article
Multidisciplinary Sciences
Wooyoung Choi, Hao Wu, Klaus Yserentant, Bo Huang, Yifan Cheng
Summary: CRISPR/Cas9-based genome engineering has greatly enhanced our ability to manipulate biological systems, and researchers have now developed a strategy to efficiently tag endogenous proteins in human cell lines using this technology. This tagging approach, combined with advancements in single-particle cryogenic electron microscopy, allows for effective structural studies of native proteins in their natural cellular environment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Hao Wu, Elise N. Munoz, Laura J. Hsieh, Un Seng Chio, Muryam A. Gourdet, Geeta J. Narlikar, Yifan Cheng
Summary: Unlike other chromatin remodelers, INO80 preferentially mobilizes hexasomes, which can form during transcription. The structures of Saccharomyces cerevisiae INO80 bound to a hexasome or a nucleosome reveal that INO80 binds the two substrates in substantially different orientations. The mechanistic adaptations used by INO80 for preferential hexasome sliding imply that subnucleosomal particles play considerable regulatory roles.
Article
Biochemical Research Methods
Kaihua Zhang, David Julius, Yifan Cheng
Summary: This protocol presents a method to capture intermediate states of nanodisc-reconstituted TRPV1 using single-particle cryo-EM, focusing on symmetry expansion and focused 3D classification. It can be applied to different proteins and samples.
Article
Biochemistry & Molecular Biology
Shawn Zheng, Georg Wolff, Garrett Greenan, Zhen Chen, Frank G. A. Faas, Montserrat Barcena, Abraham J. Koster, Yifan Cheng, David A. Agard
Summary: AreTomo is a GPU accelerated software package that automates motion correction and reconstruction of electron tomography. It can produce accurate tomograms by correcting various types of motion, including rotation, translation, and beam-induced motion. It also provides real-time feedback on sample quality and allows for adjustments of collection parameters. The study shows that accurate correction of local motion is critical for high-resolution cryo-electron tomography.
JOURNAL OF STRUCTURAL BIOLOGY-X
(2022)
Meeting Abstract
Biophysics
Digvijay Singh, Christopher W. Akey, Christna Ouch, Ignacia Echeverria, Ilona Nudelman, Joseph M. Varberg, Zulin Yu, James C. Gumbart, Sue L. Jaspersen, Brian T. Chait, Andrej Sali, Javier Fernandez-Martinez, Steven Ludtke, Michael P. Rout, Elizabeth Villa
BIOPHYSICAL JOURNAL
(2022)
