Article
Biochemistry & Molecular Biology
Duong Long Duy, Nayun Kim
Summary: Sequences capable of forming quadruplex or G4 DNA are common in promoter regions and they regulate transcription of human genes by changing secondary structure. In the yeast Saccharomyces cerevisiae, we found 37 genes with a G4 motif in the promoters, including 20 genes with both G4 motif and stress response element (STRE). The transcription factor Msn2 directly binds to G4 DNA and is enriched at G4 DNA-forming loci in yeast genome. Treating with G4-ligands significantly increases transcription levels for most genes with G4/STRE-containing promoters, but this effect is diminished when msn2 & msn4 genes are deleted or when the G4 motif is disrupted.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Bryce T. Bajar, Nguyen T. Phi, Jesse Isaacman-Beck, Jun Reichl, Harpreet Randhawa, Orkun Akin
Summary: Research has found that patterned neural activity during the development of the fruit fly's central nervous system is coordinated by a small population of neurons expressing the Trp gamma gene. This activity is essential for the formation of synaptic connections and the assembly of the brain. The study establishes the fruit fly's brain as a useful model system for investigating how neural activity contributes to the formation of synapses and circuits.
Article
Multidisciplinary Sciences
Kora-Lee Claude, Daniela Bureik, Petia Adarska, Abhyudai Singh, Kurt M. Schmoller, Dimitra Chatzitheodoridou
Summary: Biochemical reactions in cells depend on protein concentrations, which are maintained by mRNA and protein synthesis rates linked to cell volume. While most proteins follow this regulation, certain structures like genomic DNA do not scale with cell size. The study shows that histone protein levels are coupled to DNA content, even though overall mRNA and protein synthesis increase with cell volume. This coordination is achieved at the transcript level and is an intrinsic property of histone promoters, leading to a decrease in histone concentrations with cell volume but an increase with ploidy. This specific mechanism provides a way to control gene expression in response to changes in cell volume and ploidy.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Anne Loft, Soren Fisker Schmidt, Giorgio Caratti, Ulrich Stifel, Jesper Havelund, Revathi Sekar, Yun Kwon, Alba Sulaj, Kan Kau Chow, Ana Jimena Alfaro, Thomas Schwarzmayr, Nikolaj Rittig, Mads Svart, Foivos-Filippos Tsokanos, Adriano Maida, Andreas Blutke, Annette Feuchtinger, Niels Moller, Matthias Blueher, Peter Nawroth, Julia Szendroedi, Nils J. Faergeman, Anja Zeigerer, Jan Tuckermann, Stephan Herzig
Summary: This study investigates the contribution of immune cells to metabolic homeostasis during fasting in healthy subjects. It identifies the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome, and shows that lack of macrophage GR impairs induction of ketogenesis during fasting and endotoxemia. This research also highlights the direct influence of liver macrophages on ketogenesis in hepatocytes, providing insights into the immune system's role in regulating metabolic activity during inflammatory diseases and infection.
Article
Biochemistry & Molecular Biology
Sarah Khalil, Erik D. Enbody, Carolina Frankl-Vilches, Joseph F. Welklin, Rebecca E. Koch, Matthew B. Toomey, Simon Yung Wa Sin, Scott Edwards, Manfred Gahr, Hubert Schwabl, Michael S. Webster, Jordan Karubian
Summary: Carotenoid pigments play a crucial role in mate choice among vertebrates by producing red, orange, and yellow visual signals. However, the processes involved in carotenoid-based trait production remain largely unknown. In this study, we induced the production of a carotenoid-based red plumage patch in male red-backed fairywrens through testosterone elevation. We compared gene expression in the liver and feather follicles of unornamented males, testosterone-implanted males, and naturally ornamented males. Our findings suggest that testosterone regulates the expression of carotenoid-associated genes and coordinaes the complex processes underlying the production of carotenoid-based traits.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Azhar, Caoling Xu, Xue Jiang, Wenqing Li, Yuzhu Cao, Xiaoli Zhu, Xuemei Xing, Limin Wu, Jiaqi Zou, Lan Meng, Yu Cheng, Wenjie Han, Jianqiang Bao
Summary: This study reveals the crucial role of Prmt1 in the establishment and maintenance of spermatogonia, and its regulation of transcriptional homeostasis. The enrichment of Prmt1-deposited H4R3me2a mark in mouse spermatogonia has a significant impact on the transcriptomic landscape and alternative splicing pattern.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Robert M. Harmon, John Devany, Margaret L. Gardel
Summary: This study investigates the mechanism by which the actin assembly factor Dia1 guides cell positioning in multicellular tissues. The results suggest that Dia1 promotes rapid growth of cell-cell adhesions and plays a crucial role in the construction of a highly crowded monolayer. The study also finds a close correlation between Dia1 expression patterns, cell stratification, and differentiation.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Qiutan Yang, Shi-Lei Xue, Chii Jou Chan, Markus Rempfler, Dario Vischi, Francisca Mauer-Gutierrez, Takashi Hiiragi, Edouard Hannezo, Prisca Liberali
Summary: This study reveals the simultaneous occurrence of crypt formation and reduction in lumen volume in intestinal organoids derived from single cells. By developing a 3D biophysical model and utilizing multiple mechanical perturbations, it demonstrates the synergistic effects of actomyosin-driven crypt apical contraction and villus basal tension with lumen volume reduction in driving crypt morphogenesis. Additionally, a sodium/glucose cotransporter specific to differentiated enterocytes was identified, which modulates lumen volume reduction through cell swelling in the villus region.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michael Busche, M. Regina Scarpin, Robert Hnasko, Jacob O. Brunkard
Summary: The TOR protein kinase in plants regulates nucleotide synthesis and metabolic balance by promoting the activity of cytosolic phosphoribosyl pyrophosphate synthetase (PRS4). Knockout of the prs4 gene leads to embryo lethality in Arabidopsis, while silencing of PRS4 expression causes various developmental abnormalities in Nicotiana benthamiana.
Article
Multidisciplinary Sciences
Roaya S. Alqurashi, Audrey S. Yee, Taylor Malone, Sumaiah Alrubiaan, Mary W. Tam, Kai Wang, Rozena R. Nandedwalla, Wesley Field, Dalal Alkhelb, Katherine S. Given, Raghib Siddiqui, James D. Baleja, K. Eric Paulson, Amy S. Yee
Summary: This study identified a transient program of molecular and metabolic signaling in the early epileptogenic period, with a focus on Wnt signaling, metabolic reprogramming, and mTOR activation. The newly discovered molecular mechanism may provide insights for refining therapeutic strategies and attenuating recurrent seizures in epilepsy.
Article
Cell Biology
Sebastian Willenborg, David E. Sanin, Alexander Jais, Xiaolei Ding, Thomas Ulas, Julian Nuechel, Milica Popovic, Thomas MacVicar, Thomas Langer, Joachim L. Schultze, Alexander Gerbaulet, Axel Roers, Edward J. Pearce, Jens C. Bruening, Aleksandra Trifunovic, Sabine A. Eming
Summary: The study found that changes in cellular metabolism play a critical role in regulating macrophage functions during wound healing.
Article
Biochemistry & Molecular Biology
Wentao Kong, Yuanchao Qian, Philip S. Stewart, Ting Lu
Summary: Synthetic biology has demonstrated the potential to program living microorganisms for various applications. However, current engineering practices mainly focus on planktonic cells, while microbes in nature constantly alternate their lifestyles. This study presents a synthetic genetic program that regulates bacterial life cycle and enables phase-specific gene expression. The program utilizes an engineered protein as the biofilm matrix building block and allows controlled biofilm assembly and decomposition as well as responsive planktonic-biofilm phase transition. By coupling with synthesis modules, it can be programmed for various functional realizations. This work establishes a versatile platform for microbial engineering and gene circuit applications in complex environments.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Andrew G. Wang, Minjun Son, Emma Kenna, Nicholas Thom, Savas Tay
Summary: This study systematically profiles the NF-KB response to different signal sequences using high-throughput microfluidic live-cell analysis. The results show that the NF-KB dynamics store the short-term history of received signals and encode information about the identity and dose of the prior stimulus. This research provides insights into how signal transduction networks process inflammatory stimuli to coordinate cellular responses.
Article
Biochemistry & Molecular Biology
Melanie Worley, Nicholas J. Everetts, Riku Yasutomi, Rebecca J. Chang, Shrey Saretha, Nir Yosef, Iswar K. Hariharan
Summary: In this study, two regeneration-specific cell populations, Blastema1 and Blastema2, were identified in the regenerating wing discs of Drosophila. These cells upregulate multiple genes encoding secreted proteins that promote regeneration. The transcription factor Ets21C was found to orchestrate a regeneration-specific gene regulatory network, and its function was shown to be essential for maintaining the expression of downstream genes and promoting successful regeneration. Additionally, similar cell populations were found in tumor discs, indicating that mechanisms involved in regeneration can be co-opted by tumors for aberrant growth.
Article
Multidisciplinary Sciences
R. Ichijo, M. Kabata, H. Kidoya, F. Muramatsu, R. Ishibashi, K. Abe, K. Tsutsui, H. Kubo, Y. Iizuka, S. Kitano, H. Miyachi, Y. Kubota, H. Fujiwara, A. Sada, T. Yamamoto, F. Toyoshima
Summary: This study uncovers the regulation of stem cells in dynamic skin, specifically in the context of epidermal proliferation and differentiation during pregnancy, and how the skin adjusts its size in coordination with dermal constituents.
Article
Multidisciplinary Sciences
Jeffrey J. Quinn, Matthew G. Jones, Ross A. Okimoto, Shigeki Nanjo, Michelle M. Chan, Nir Yosef, Trever G. Bivona, Jonathan S. Weissman
Summary: This study used a Cas9-based lineage tracer to track the development and metastasis of lung cancer cells in a mouse model over months, revealing heterogeneity in metastatic capacity and genetic differences that drive invasiveness. The study also uncovered some genes driving metastasis and an unexpected suppressive role of KRT17 in metastasis.
Article
Oncology
Yuan-Hung Lo, Kevin S. Kolahi, Yuhong Du, Chiung-Ying Chang, Andrey Krokhotin, Ajay Nair, Walter D. Sobba, Kasper Karlsson, Sunny J. Jones, Teri A. Longacre, Amanda T. Mah, Bahar Tercan, Alexandra Sockell, Hang Xu, Jose A. Seoane, Jin Chen, Ilya Shmulevich, Jonathan S. Weissman, Christina Curtis, Andrea Califano, Haian Fu, Gerald R. Crabtree, Calvin J. Kuo
Summary: Mutations in ARID1A are common in human cancer, but the oncogenic consequences of these mutations remain unclear. Using CRISPR/Cas9, researchers induced dysplasia, tumorigenicity, and mucinous differentiation in human gastric organoids, providing insights into the pathways affected by ARID1A mutation. Further analysis showed vulnerability of ARID1A-deficient organoids to inhibition of BIRC5/survivin, highlighting this pathway as crucial for early-stage gastric tumorigenesis.
Article
Cell Biology
Kuanqing Liu, Daniel A. Santos, Jeffrey A. Hussmann, Yun Wang, Benjamin M. Sutter, Jonathan S. Weissman, Benjamin P. Tu
Summary: N-6-methyladenosine (m(6)A) is a conserved ribonucleoside modification that regulates RNA metabolism. This study found that tandem adenosines at the 3' end of 18S rRNA are also methylated, with significantly increased levels in response to sulfur starvation. Ribosomes with m(6)A were shown to have distinct translation preferences for sulfur metabolism genes.
Article
Biochemistry & Molecular Biology
James K. Nunez, Jin Chen, Greg C. Pommier, J. Zachery Cogan, Joseph M. Replogle, Carmen Adriaens, Gokul N. Ramadoss, Quanming Shi, King L. Hung, Avi J. Samelson, Angela N. Pogson, James Y. S. Kim, Amanda Chung, Manuel D. Leonetti, Howard Y. Chang, Martin Kampmann, Bradley E. Bernstein, Volker Hovestadt, Luke A. Gilbert, Jonathan S. Weissman
Summary: CRISPRoff is a programmable epigenetic memory writer that can heritably alter gene expression by initiating specific DNA methylation and gene repression. The tool utilizes a single dead Cas9 fusion protein to establish these modifications, which are maintained through cell division and differentiation processes. By pairing CRISPRoff with genome-wide screens and analysis of chromatin marks, rules for heritable gene silencing can be established, with the tool capable of targeting a wide range of genes beyond canonical CpG islands.
Article
Biochemistry & Molecular Biology
Xiaojie Qiu, Yan Zhang, Jorge D. Martin-Rufino, Chen Weng, Shayan Hosseinzadeh, Dian Yang, Angela N. Pogson, Marco Y. Hein, Kyung Hoi (Joseph) Min, Li Wang, Emanuelle Grody, Matthew J. Shurtleff, Ruoshi Yuan, Song Xu, Yian Ma, Joseph M. Replogle, Eric S. Lander, Spyros Darmanis, Ivet Bahar, Vijay G. Sankaran, Jianhua Xing, Jonathan S. Weissman
Summary: This article introduces an analytical framework called dynamo, which combines single-cell RNA-seq, RNA velocity, and metabolic labeling to reveal cellular states and transitions. It can predict cell fates and perturbation outcomes, and overcome the limitations of conventional splicing-based RNA velocity analyses.
Article
Biotechnology & Applied Microbiology
Marco Y. Hein, Jonathan S. Weissman
Summary: Understanding the roles of viral and host factors in human cytomegalovirus infection was explored using CRISPR interference and nuclease screening. The study revealed how perturbations of critical host and viral factors can alter the progression and timing of infection. Results showed that perturbing host factors can impact the stage of infection, while perturbation of viral factors can lead to distinct infection trajectories.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Avi J. Samelson, Quang Dinh Tran, Remy Robinot, Lucia Carrau, Veronica V. Rezelj, Alice Mac Kain, Merissa Chen, Gokul N. Ramadoss, Xiaoyan Guo, Shion A. Lim, Irene Lui, James K. Nunez, Sarah J. Rockwood, Jianhui Wang, Na Liu, Jared Carlson-Stevermer, Jennifer Oki, Travis Maures, Kevin Holden, Jonathan S. Weissman, James A. Wells, Bruce R. Conklin, Benjamin R. TenOever, Lisa A. Chakrabarti, Marco Vignuzzi, Ruilin Tian, Martin Kampmann
Summary: The protein BRD2 is found to be crucial for ACE2 transcription and SARS-CoV-2 infection in human lung epithelial cells and cardiomyocytes. BRD2 inhibitors can effectively block endogenous ACE2 expression and viral infection in human cells, including nasal epithelial cells. Furthermore, inhibiting BRD2 with a drug called ABBV-744 can suppress SARS-CoV-2 replication in Syrian hamsters. BRD2 also controls the transcription of several other genes induced by SARS-CoV-2 infection, including the interferon response, which regulates the antiviral response.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Noa Dahan, Yury S. Bykov, Elizabeth A. Boydston, Amir Fadel, Zohar Gazi, Hodaya Hochberg-Laufer, James Martenson, Vlad Denic, Yaron Shav-Tal, Jonathan S. Weissman, Naama Aviram, Einat Zalckvar, Maya Schuldiner
Summary: This study discovered that translation of specific peroxisomal membrane proteins (PMPs) occurs on the surface of peroxisomes in yeast, similar to chloroplasts, mitochondria, and the endoplasmic reticulum. This localized translation process ensures the correct insertion of hydrophobic proteins into the peroxisomal membrane. Proper targeting of PMP transcripts to peroxisomes is crucial for cellular and peroxisomal function, highlighting the importance of localized translation in cellular physiology.
Article
Biochemistry & Molecular Biology
Dian Yang, Matthew G. Jones, Santiago Naranjo, William M. Rideout III, Kyung Hoi (Joseph) Min, Raymond Ho, Wei Wu, Joseph M. Replogle, Jennifer L. Page, Jeffrey J. Quinn, Felix Horns, Xiaojie Qiu, Michael Z. Chen, William A. Freed-Pastor, Christopher S. McGinnis, David M. Patterson, Zev J. Gartner, Eric D. Chow, Trever G. Bivona, Michelle M. Chan, Nir Yosef, Tyler Jacks, Jonathan S. Weissman
Summary: Tumor evolution is driven by progressive genetic and epigenetic alterations, enabling unrestricted growth and expansion. This study provides insights into the hierarchical nature of tumor evolution through tracking phylogenetic relationships between cancer cells, allowing for in-depth studies of tumor progression.
Article
Multidisciplinary Sciences
Nathan H. Cho, Keith C. Cheveralls, Andreas-David Brunner, Kibeom Kim, Andre C. Michaelis, Preethi Raghavan, Hirofumi Kobayashi, Laura Savy, Jason Y. Li, Hera Canaj, James Y. S. Kim, Edna M. Stewart, Christian Gnann, Frank McCarthy, Joana P. Cabrera, Rachel M. Brunetti, Bryant B. Chhun, Greg Dingle, Marco Y. Hein, Bo Huang, Shalin B. Mehta, Jonathan S. Weissman, Rafael Gomez-Sjoberg, Daniel N. Itzhak, Loic A. Royer, Matthias Mann, Manuel D. Leonetti
Summary: This article introduces a method that uses various techniques to systematically map the localization and interactions of human proteins, and discovers the rich functional information contained in protein localization patterns.
Review
Cell Biology
Bradley W. Wright, Zixin Yi, Jonathan S. Weissman, Jin Chen
Summary: Omics-based technologies have revealed the existence of unannotated open reading frames (ORFs) in genomes, which have the potential to encode novel functional proteins or have regulatory roles. However, there is still limited understanding of these noncanonical ORFs in the scientific community, despite the few that have been studied and shown to play important roles in biological processes.
TRENDS IN CELL BIOLOGY
(2022)
Article
Geriatrics & Gerontology
Tyler A. U. Hilsabeck, Ru Liu-Bryan, Tracy Guo, Kenneth A. Wilson, Neelanjan Bose, Daniel Raftery, Jennifer N. Beck, Sven Lang, Kelly Jin, Christopher S. Nelson, Tal Oron, Marshall Stoller, Daniel Promislow, Rachel B. Brem, Robert Terkeltaub, Pankaj Kapahi
Summary: The study identifies the role of mda/FAM214A gene in regulating purine metabolism and its contribution to diseases caused by hyperuricemia and tissue inflammation. It suggests mda/FAM214A as a potential novel target for uric acid-driven pathologies.
Article
Biochemistry & Molecular Biology
Joseph M. Replogle, Reuben A. Saunders, Angela N. Pogson, Jeffrey A. Hussmann, Alexander Lenail, Alina Guna, Lauren Mascibroda, Eric J. Wagner, Karen Adelman, Gila Lithwick-Yanai, Nika Iremadze, Florian Oberstrass, Doron Lipson, Jessica L. Bonnar, Marco Jost, Thomas M. Norman, Jonathan S. Weissman
Summary: Understanding the relationships between genotypes and phenotypes is a central goal in genetics. This study demonstrates the use of a high-content phenotypic screening technique, Perturb-seq, to analyze over 2.5 million human cells at a genome-wide scale. Through this analysis, new gene functions and complex cellular phenomena were revealed.
Article
Biotechnology & Applied Microbiology
Fulong Yu, Liam D. Cato, Chen Weng, L. Alexander Liggett, Soyoung Jeon, Keren Xu, Charleston W. K. Chiang, Joseph L. Wiemels, Jonathan S. Weissman, Adam J. de Smith, Vijay G. Sankaran
Summary: Genome-wide association studies combined with single-cell genomic atlases can reveal the mechanisms of disease-causal genetic variations. However, sparse and noisy single-cell epigenomic data analysis often hinders the identification of disease-relevant cell types. To overcome this, the SCAVENGE algorithm uses network propagation to map causal variants to their relevant cellular context at a single-cell resolution, successfully identifying key biological mechanisms in various blood traits and diseases.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Christoph Bock, Paul Datlinger, Florence Chardon, Matthew A. Coelho, Matthew B. Dong, Keith A. Lawson, Tian Lu, Laetitia Maroc, Thomas M. Norman, Bicna Song, Geoff Stanley, Sidi Chen, Mathew Garnett, Wei Li, Jason Moffat, Lei S. Qi, Rebecca S. Shapiro, Jay Shendure, Jonathan S. Weissman, Xiaowei Zhuang
Summary: CRISPR screens are a powerful tool for unbiased investigation of gene functions in various applications and species. By introducing genetically encoded perturbations into cell pools, these screens allow the evaluation of gene effects under biological challenges. High-content read-outs and dedicated software tools enhance the analysis and reproducibility of the results, making it a flexible and reliable method for biological discovery and drug development.
NATURE REVIEWS METHODS PRIMERS
(2022)