Article
Biochemistry & Molecular Biology
Tessa Swain, Christian Pflueger, Saskia Freytag, Daniel Poppe, Jahnvi Pflueger, Trung Viet Nguyen, Ji Kevin Li, Ryan Lister
Summary: The SSSavi system is a modular combinatorial epigenome editing platform that allows precise editing of chromatin contexts by controlling the combination and spatial order of effector recruitment.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Henriette O'Geen, Marketa Tomkova, Jacquelyn A. Combs, Emma K. Tilley, David J. Segal
Summary: This study systematically investigated the ability of CRISPR/dCas9-based epigenome editors to engineer persistent epigenetic silencing. It revealed the importance of cis regulatory features and chromatin marks in the stability of epigenetic reprogramming, providing insights into engineering predictable and long-lasting gene expression changes.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Muneaki Nakamura, Yuchen Gao, Antonia A. Dominguez, Lei S. Qi
Summary: The review discusses CRISPR-based epigenome engineering technologies for modulating histone and DNA modifications, perturbing DNA and RNA regulatory elements, and chromatin organization. The epigenome involves complex cellular processes governing genomic activity. Repurposing prokaryotic CRISPR systems has enabled the development of diverse technologies in epigenome engineering.
NATURE CELL BIOLOGY
(2021)
Article
Oncology
Hua Huang, Wen Zhang, Jian Zhang, Anshun Zhao, Hongwei Jiang
Summary: Recently, Leydig cell (LCs) transplantation has shown promise in treating male hypogonadism. However, the limited availability of seed cells has hindered its application. This study aimed to optimize the CRISPR/dCas9 system for transdifferentiating human foreskin fibroblasts (HFFs) into Leydig-like cells(iLCs). By using advanced dCas9p300, the generation of iLCs was facilitated, resulting in higher expression of steroidogenic biomarkers and increased testosterone production. Additionally, preferred enrichment in H3K27ac at the promoters was observed only with dCas9p300 treatment. These findings suggest that the improved version of dCas9 can enhance the harvesting of iLCs, providing sufficient seed cells for cell transplantation treatment of androgen deficiency in the future.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Biophysics
Saba Safdar, Seppe Driesen, Karen Leirs, Delphine De Sutter, Sven Eyckerman, Jeroen Lammertyn, Dragana Spasic
Summary: In recent years, CRISPR-Cas-based technologies have gained increasing attention in the biosensing field. Researchers have successfully integrated flexible signal generation and amplification properties into the CRISPR-dCas9 complex by incorporating a DNA sequence, allowing for the detection of nucleic acid targets.
BIOSENSORS & BIOELECTRONICS
(2022)
Editorial Material
Biochemical Research Methods
Nina Vogt
Summary: Prime editors allow for precise introduction of different types of small mutations into genomes.
Article
Biochemistry & Molecular Biology
Xianrong Xie, Fuquan Li, Xiyu Tan, Dongchang Zeng, Weizhi Liu, Wanyong Zeng, Qinlong Zhu, Yao-Guang Liu
Summary: This study presents a user-friendly web tool named BEtarget for designing gRNAs for base editing. The tool supports various functions and can be used in different types of genomes.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Oncology
Imran Ansari, Animesh Chaturvedi, Deepak Chitkara, Saurabh Singh
Summary: The understanding of the relationship between epigenetic alterations and gene expression have opened up new therapeutic pathways for treating various diseases, including cancer. CRISPR/Cas and other genome editing technologies have shown potential in epigenome editing. This review outlines the epigenetic therapeutic approach using CRISPR/Cas for cancer therapy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Cell Biology
Chengkun Wang, Yuanhao Qu, Jason K. W. Cheng, Nicholas W. Hughes, Qianhe Zhang, Mengdi Wang, Le Cong
Summary: The researchers developed a genome-editing system using catalytically inactive Cas9 fused with microbial single-strand annealing proteins, allowing for kilobase-scale insertion in human cells without DNA nicks or breaks. The system, called dCas9-SSAP, demonstrates low on-target errors and minimal off-target effects, making it more accurate than traditional Cas9 methods. It is highly efficient in inserting long sequences and works well in various cell types.
NATURE CELL BIOLOGY
(2022)
Article
Biochemical Research Methods
Matthew Gemberling, Keith Siklenka, Erica Rodriguez, Katherine R. Tonn-Eisinger, Alejandro Barrera, Fang Liu, Ariel Kantor, Liqing Li, Valentina Cigliola, Mariah F. Hazlett, Courtney Williams, Luke C. Bartelt, Victoria J. Madigan, Josephine Bodle, Heather Daniels, Douglas C. Rouse, Isaac B. Hilton, Aravind Asokan, Maria Ciofani, Kenneth D. Poss, Timothy E. Reddy, Anne E. West, Charles A. Gersbach
Summary: Two conditional transgenic mouse lines based on CRISPRa and CRISPRi enable epigenome editing in vivo.
Article
Biochemistry & Molecular Biology
Min Wang, Li He, Bowei Chen, Yanwei Wang, Lishan Wang, Wei Zhou, Tianxu Zhang, Lesheng Cao, Peng Zhang, Linan Xie, Qingzhu Zhang
Summary: The CRISPR/dCas9-TET1cd system can be used to target hypermethylated DNA regions, reducing methylation levels and increasing gene expression, leading to accelerated leaf senescence. The edited methylation status shows stable transgenerational transmission, providing a rational approach for editing spontaneously mutated epialleles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kira M. Veley, Kiona Elliott, Greg Jensen, Zhenhui Zhong, Suhua Feng, Marisa Yoder, Kerrigan B. Gilbert, Jeffrey C. Berry, Zuh-Jyh Daniel Lin, Basudev Ghoshal, Javier Gallego-Bartolome, Joanna Norton, Sharon Motomura-Wages, James C. Carrington, Steven E. Jacobsen, Rebecca S. Bart
Summary: The targeted methylation at the TAL20 effector binding element of the cassava SWEET10a gene leads to resistance to Xanthomonas phaseoli. This study demonstrates that blocking access to host susceptibility (S) genes through targeted methylation can increase disease resistance.
NATURE COMMUNICATIONS
(2023)
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.
Review
Biochemistry & Molecular Biology
Raghul Senthilnathan, Ilamathi Ilangovan, Milind Kunale, Nalini Easwaran, Siva Ramamoorthy, Ashokkumar Veeramuthu, Gothandam Kodiveri Muthukaliannan
Summary: Gene editing techniques, especially CRISPR, have revolutionized the field of Genetic engineering due to their simplicity and effectiveness in editing a wide range of organisms. This review focuses on assessing the mutagenesis mediated by Cas12 systems and elucidating their editing efficacy in various species. Furthermore, it highlights the experimental benefits and applications of Cas12 systems.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Cell Biology
Junming Qian, Xiaonan Guan, Bing Xie, Chuanyun Xu, Jacqueline Niu, Xin Tang, Charles H. Li, Henry M. Colecraft, Rudolf Jaenisch, X. Shawn Liu
Summary: Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations of MECP2. Researchers successfully used epigenome editing techniques to reactivate the silent wild-type MECP2 allele from the inactive X chromosome in RTT hESCs and derived neurons. This reactivation reversed the characteristics of RTT and provided a proof-of-concept study for using epigenome editing to treat RTT and potentially other dominant X-linked diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Bram Henneman, Thomas B. Brouwer, Amanda M. Erkelens, Gert-Jan Kuijntjes, Clara van Emmerik, Ramon A. van der Valk, Monika Timmer, Nancy C. S. Kirolos, Hugo van Ingen, John van Noort, Remus T. Dame
Summary: Archaea express histones which play a key role in organizing the genome and gene regulation, forming hypernucleosomes that depend on stacking interactions, torque, and force for stability. The assembly of hypernucleosomes on long DNA substrates is facilitated by cooperative binding of histones to DNA. In response to environmental changes, modulation of the archaeal hypernucleosome structure may be important for transcription regulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Fredj Ben Bdira, Amanda M. Erkelens, Liang Qin, Alexander N. Volkov, Andrew M. Lippa, Nicholas Bowring, Aimee L. Boyle, Marcellus Ubbink, Simon L. Dove, Remus T. Dame
Summary: H-NS family proteins play important roles in genome organization and regulation of foreign genes, with gene repression directly dependent on their DNA binding modes. The protein gp4 encoded by Pseudomonas lytic phage LUZ24 can specifically interfere with the formation and stability of the bridged MvaT-DNA complex, relieving gene silencing and adversely affecting P. aeruginosa growth. Controlling H-NS conformation may provide new ways to combat Pseudomonas multidrug resistance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Szu-Ning Lin, Remus T. Dame, Gijs J. L. Wuite
Summary: Architectural DNA-binding proteins, such as HU, play a crucial role in DNA transactions. This study investigates how ionic conditions affect the interaction between HU and DNA, revealing different binding and diffusion behaviors of HU under various conditions. Additionally, the effect of DNA tension on HU-DNA complexes is explored, with tension above 50 pN resulting in increased binding affinity attributed to force-induced structural changes in DNA.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Benjamin R. Gilbert, Zane R. Thornburg, Vinson Lam, Fatema-Zahra M. Rashid, John Glass, Elizabeth Villa, Remus T. Dame, Zaida Luthey-Schulten
Summary: JCVI-syn3A is a genetically minimal bacterial cell with a small genome, allowing for unique opportunities in whole-cell modeling. Cell structures of Syn3A were reconstructed from cryo-electron tomograms, and chromosome contact maps were predicted based on simulated chromosome configurations.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Fatema-Zahra M. Rashid, Eike Mahlandt, Michiel van der Vaart, Daphne E. C. Boer, Monica Varela Alvarez, Bram Henneman, Daan J. W. Brocken, Patrick Voskamp, Anneloes J. Blok, Thomas S. Shimizu, Annemarie H. Meijer, Martijn S. Luijsterburg, Joachim Goedhart, Frederic G. E. Cremazy, Remus T. Dame
Summary: The interplay between three-dimensional chromosome organisation and genomic processes requires in vivo studies. However, the use of fluorescent organic dyes for chromosome labelling can cause structural changes in DNA, leading to interference with gene expression, genome replication, and cell cycle progression. Researchers have developed a minimally-perturbing, genetically encoded fluorescent DNA label that effectively labels chromosomes in eukaryotic cells and zebrafish embryos.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Microbiology
Remus T. Dame
Article
Multidisciplinary Sciences
David Forrest, Emily A. Warman, Amanda M. Erkelens, Remus T. Dame, David C. Grainger
Summary: Bacteria employ silencing proteins to prevent improper transcription of horizontally acquired DNA, with differences in strategies between E. coli and Bacillus subtilis due to the specificities of the silencing protein and RNA polymerase in each organism.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Chao Du, Joost Willemse, Amanda M. Erkelens, Victor J. Carrion, Remus T. Dame, Gilles P. van Wezel
Summary: This study identified a novel nucleoid-associated protein (NAP), Gbn, in Actinobacteria that binds to GATC sequences and plays a significant role in the growth and development of Streptomyces. Gbn has broad effects on global gene expression during the late developmental stage.
Article
Chemistry, Inorganic & Nuclear
Corjan van de Griend, Johannes J. van de Vijver, Maxime A. Siegler, Remus T. Dame, Sylvestre Bonnet
Summary: This study investigates the coordination of tetradentate ligands to metal centers and the resulting formation of helical chiral complexes. The inversion barrier of these complexes is studied using variable-temperature H-1 NMR. Additionally, a serendipitous ring-closing reaction is discovered, resulting in the formation of a chiral complex. This unexpected transformation appears to be specific to ruthenium(II) as macrocyclization did not occur with other metals.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Amanda M. Erkelens, Liang Qin, Bert van Erp, Andres Miguel-Arribas, David Abia, Helena G. J. Keek, Dorijn Markus, Marc K. M. Cajili, Samuel Schwab, Wilfried J. J. Meijer, Remus T. Dame
Summary: The study demonstrates that Rok is a DNA bridging protein similar to prototypical H-NS-like proteins, but its bridging ability is not affected by changes in physico-chemical conditions. The DNA binding properties of Rok's interaction partner sRok are affected by salt concentration, suggesting that Rok's activity may respond indirectly to environmental stimuli through sRok.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Fatema-Zahra M. Rashid, Remus T. Dame
Summary: Nucleoid-associated proteins (NAPs) are bacterial architectural proteins and transcription factors that regulate gene expression in response to environmental signals. However, the coupling between their structural and regulatory functions in vivo is still uncertain. This study focuses on the NAP H-NS, proposing it as a sensor-effector protein that directly remodels chromatin to regulate gene expression. The findings suggest that the interplay between chromosome structure and gene expression may be an underappreciated concept in bacterial transcription regulation.
MOLECULAR MICROBIOLOGY
(2023)
Meeting Abstract
Biophysics
Fatema Zahra M. Rashid, Kathy R. Chaurasiya, Daan J. W. Brocken, Remus T. Dame
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Mandy Erkelens, Bram Henneman, Thomas B. Brouwer, Gert-Jan A. J. T. Kuijntjes, Clara van Emmerik, Ramon A. van der Valk, Monika Timmer, Nancy C. S. Kirolos, Hugo van Ingen, John Van Noort, Remus T. Dame
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Benjamin R. Gilbert, Zane R. Thornburg, Vinson Lam, Elizabeth Villa, Fatema Zahra M. Rashid, Remus T. Dame, Zaida Luthey-Schulten
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Fredj Ben Bdira, Liang Qing, Alexander N. Volkov, Mandy Erkelens, Remus T. Dame
BIOPHYSICAL JOURNAL
(2021)