Article
Biochemistry & Molecular Biology
Zhengyu Luo, Ran Zhang, Tengfei Hu, Yuting Zhu, Yueming Wu, Wenfei Li, Zhi Zhang, Xuebiao Yao, Haiyi Liang, Xiaoyuan Song
Summary: The study introduces a new method called NicE-C, which allows for the detection of open chromatin interactions, particularly enhancer-promoter interactions, at a high resolution, with stability and cost-effectiveness. Using this method, the researchers revealed characteristics of dynamic enhancer-promoter interactions in TNF stimulation and mouse kidney aging models.
Article
Multidisciplinary Sciences
Qiaoni Yu, Xu Liu, Jingwen Fang, Huihui Wu, Chuang Guo, Wen Zhang, Nianping Liu, Chen Jiang, Qing Sha, Xiao Yuan, Zhikai Wang, Kun Qu
Summary: Although mitotic chromosomes are highly compacted and transcriptionally inert, some active chromatin features are retained during mitosis, referred to as mitotic bookmarking, to ensure proper postmitotic reestablishment of maternal transcriptional programs. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), this study found that chromatin accessibility changes throughout cell division, with a constant decrease until metaphase and a gradual increase as chromosomes segregate. Certain chromatin regions remain open throughout mitosis, and genes associated with these bookmarked regions are quickly reactivated upon mitotic exit. The nuclear transcription factor Y subunit alpha (NF-YA) plays a role in transcriptional reactivation after mitosis.
Article
Genetics & Heredity
Sara Rodriguez, Ashley Ward, Andrew T. Reckard, Yulia Shtan, Clayton Hull-Crew, Andrew D. Klocko
Summary: The precise organization of the eukaryotic genome is crucial for its proper functioning, and disruptions to genome topology can lead to diseases. High-resolution Hi-C datasets provide valuable insights into the folding principles of individual genes. In this study, the genome topology of the fungal model organism Neurospora crassa is reported, providing valuable insights into higher organism genome topology.
G3-GENES GENOMES GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
Zsolt Banfai, Erzsebet Koevesdi, Katalin Suemegi, Gergely Bueki, Andras Szabo, Lili Magyari, Valerian adam, Ferenc Palos, Attila Miseta, Miklos Kasler, Bela Melegh
Summary: This study provides the first analysis of the genetic composition of the Danube Swabians based on genome-wide autosomal data. The results suggest that they have significant German and other West European ancestry, with a prominent Hungarian ancestry.
Article
Biochemical Research Methods
Spiro C. Stilianoudakis, Maggie A. Marshall, Mikhail G. Dozmorov
Summary: The preciseTAD framework, trained on high-resolution genome annotation data, accurately predicts 3D domain boundaries at base-pair resolution, providing a new tool for better understanding how genomic regulators shape the 3D structure of the genome.
Article
Biotechnology & Applied Microbiology
Stephen Bevan, Stefan Schoenfelder, Robert J. Young, Lin Zhang, Simon Andrews, Peter Fraser, Peter M. O'Callaghan
Summary: Chinese hamster ovary (CHO) cell lines are crucial for the biopharmaceutical industry, but their unstable transgene expression poses challenges. This study presents a 3D genome map of CHOK1SV (R) 10E9 cell line and an improved genome assembly, enhancing understanding of the CHO genome organization. Our findings reveal higher order chromatin structures and assist in identifying regulatory elements, ultimately improving transgene integration and cell line development.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Multidisciplinary Sciences
Cheng-Yong Tham, LaiFong Poon, TingDong Yan, Javier Yu Peng Koh, Muhammad Khairul Ramlee, Vania Swee Imm Teoh, Suihan Zhang, Yi Cai, Zebin Hong, Gina S. S. Lee, Jin Liu, Hai Wei Song, William Ying Khee Hwang, Bin Tean Teh, Patrick Tan, Lifeng Xu, Angela S. Koh, Motomi Osato, Shang Li
Summary: The authors developed a method using single-molecule real-time (SMRT) sequencing to capture and accurately analyze the length of telomeres, addressing challenges in quantifying telomere length at the nucleotide level. Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes, and their progressive shortening is a promising biomarker for age-associated diseases. The workflow involved capturing telomeres using new telobaits and measuring their length accurately with high resolution using SMRT sequencing. Results showed the heterogeneity of telomeric variant sequences (TVSs), which disrupt the continuity of the canonical telomere repeats and affect telomere protection.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dexi Bi, Yin Zhu, Yaohui Gao, Hao Li, Xingchen Zhu, Rong Wei, Ruting Xie, Chunmiao Cai, Qing Wei, Huanlong Qin
Summary: This study identified Fusobacterium species and subspecies in CRC patient samples using a new sequencing method. They found that certain species are associated with CRC in tumor samples and feces. Additionally, different Fusobacterium lineages may play different functional roles in CRC.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Roxanna S. Ramnarine-Sanchez, Janos M. Kanczler, Nicholas D. Evans, Richard O. C. Oreffo, Jonathan I. Dawson
Summary: This paper reports a new reaction-diffusion self-assembly system, in which proteins function as diffusive reactants to assemble stable clay-protein composite hydrogels. Using this method, scalable and highly stable 3D protein patterns can be generated at sub-cellular resolution, and can guide cell behavior to achieve precise bone tissue template formation.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Damien J. Downes, Robert A. Beagrie, Matthew E. Gosden, Jelena Telenius, Stephanie J. Carpenter, Lea Nussbaum, Sara De Ornellas, Martin Sergeant, Chris Q. Eijsbouts, Ron Schwessinger, Jon Kerry, Nigel Roberts, Arun Shivalingam, Afaf El-Sagheer, A. Marieke Oudelaar, Tom Brown, Veronica J. Buckle, James O. J. Davies, Jim R. Hughes
Summary: This study demonstrates the Nuclear-Titrated Capture-C method for generating high-resolution genome-wide interaction profiles, overcoming limitations of current 3C methods.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ting Wu, Danli Jiang, Meijuan Zou, Wei Sun, Di Wu, Jing Cui, Ian Huntress, Xinxia Peng, Gang Li
Summary: This study utilized Reel-seq and FREP-MS analysis techniques to systematically identify cis-regulatory elements (cis-REs) at high resolution in the human genome, revealing their role in regulating gene expression by recruiting specific proteins and transcription factors, thereby impacting cellular senescence.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Shanshan Zhang, Dylan Plummer, Leina Lu, Jian Cui, Wanying Xu, Miao Wang, Xiaoxiao Liu, Nachiketh Prabhakar, Jatin Shrinet, Divyaa Srinivasan, Peter Fraser, Yan Li, Jing Li, Fulai Jin
Summary: DeepLoop is a modular Hi-C processing workflow that enables robust chromatin interaction mapping from low-depth Hi-C data through deep-learning-based signal enhancement. It can identify allele-specific chromatin loops and structural variants, providing loop-resolution insights into the genetics of the three-dimensional genome.
Article
Multidisciplinary Sciences
Fan Feng, Yuan Yao, Xue Qing David Wang, Xiaotian Zhang, Jie Liu
Summary: While large-scale 3D genome architecture is well studied, the authors developed a deep learning model CAESAR to map 1D epigenomic profiles to fine-scale 3D chromatin structures, accurately predicting structures that were missed by Hi-C datasets. They successfully imputed high-resolution 3D chromatin contact maps for 91 human tissues and cell lines, demonstrating the potential of CAESAR in coupling transcriptional regulation with 3D chromatin organization at high resolution.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Jeffrey Demas, Jason Manley, Frank Tejera, Kevin Barber, Hyewon Kim, Francisca Martinez Traub, Brandon Chen, Alipasha Vaziri
Summary: Two-photon microscopy has enabled high-resolution imaging of neuroactivity within scattering brain tissue, but there are still tradeoffs between speed and spatiotemporal sampling. Light beads microscopy (LBM) introduces a scalable and spatiotemporally optimal acquisition approach for recording neuroactivity at different scales, offering opportunities for discovering neurocomputations in the mammalian brain.
Article
Multidisciplinary Sciences
Dashiell J. Massey, Amnon Koren
Summary: This study uses high throughput sequencing of individual cells to reveal the variability in DNA replication initiation and progression. The results show that initiation sites are mainly concentrated in specific genomic regions, and the firing order is similar but not strictly deterministic across cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kelly Cochran, Divyanshi Srivastava, Avanti Shrikumar, Akshay Balsubramani, Ross C. Hardison, Anshul Kundaje, Shaun Mahony
Summary: The DNA sequence preferences and cooperative partners of transcription factors (TFs) are conserved across species. However, predicting TF binding in one species based on sequence models of a closely related species is challenging due to species-specific repeats. To address this challenge, researchers used neural networks to predict TF binding across species and found that the predictive performance was worse than within-species predictions. By using an augmented network architecture, they were able to correct for prediction errors caused by species-specific repeats and improve the overall cross-species model performance.
Editorial Material
Hematology
Ross C. Hardison
Summary: In this study, Topfer et al use a combination of natural history and modern genome editing techniques to provide evidence for the role of promoter competition in the switching of hemoglobin production. Their findings offer promising therapeutic approaches for inherited hemoglobin disorders and resolve a long-standing issue, proposing a unifying model.
Article
Biochemistry & Molecular Biology
Liyan Fan, David R. Sweet, Erica K. Fan, Domenick A. Prosdocimo, Annmarie Madera, Zhen Jiang, Roshan Padmanabhan, Saptarsi M. Haldar, Vinesh Vinayachandran, Mukesh K. Jain
Summary: Skeletal muscle dynamically regulates systemic nutrient homeostasis through transcriptional adaptations. KLF15, a zinc-finger transcription factor, plays a critical role in metabolic adaptation by binding to distal intergenic regions and regulating genes related to circadian rhythmicity and lipid metabolism. KLF15 and PPAR delta have interdependent interactions and co-regulate lipid metabolic gene programs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Gorkem Garipler, Congyi Lu, Alexis Morrissey, Lorena S. Lopez-Zepeda, Yingzhen Pei, Simon E. Vidal, Ana Paula Zen Petisco Fiore, Begum Aydin, Matthias Stadtfeld, Uwe Ohler, Shaun Mahony, Neville E. Sanjana, Esteban O. Mazzoni
Summary: The transcription factors ZBTB11 and ZFP131 are essential for maintaining pluripotency in embryonic stem cells. They repress the premature expression of pro-differentiation genes, preventing the loss of pluripotency.
Article
Genetics & Heredity
Vinesh Vinayachandran, Purnima Bhargava
Summary: This study found that the small non-histone protein Nhp6 in budding yeast specifically influences the transcription of the SNR6 gene. The absence of Nhp6 or disruption of the T-7 sequence leads to downstream initiation of transcription. Additionally, the relative rotational orientation of the promoter elements in nucleosomal DNA and Nhp6 regulate the transcription of the SNR6 gene with precision.
FRONTIERS IN GENETICS
(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.
Article
Cell Biology
Lalitha Nayak, David R. Sweet, Asha Thomas, Stephanie D. Lapping, Kenneth Kalikasingh, Annmarie Madera, Vinesh Vinayachandran, Roshan Padmanabhan, Neelakantan T. Vasudevan, Jay T. Myers, Alex Y. Huang, Alvin Schmaier, Nigel Mackman, Xudong Liao, Andrei Maiseyeu, Mukesh K. Jain
Summary: Arterial and venous thrombosis are major global diseases with common mechanisms involving neutrophils. This study identified neutrophils as key effectors in thrombosis and demonstrated the feasibility of targeting them using immunoregulatory nanoparticles. Moreover, key molecular events and regulators of neutrophil activation were identified, providing potential targets for therapeutics against immunothrombosis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Liyan Fan, Alexander F. Lesser, David R. Sweet, Komal S. Keerthy, Yuan Lu, Ernest R. Chan, Vinesh Vinayachandran, Olga Ilkayeva, Tapatee Das, Christopher B. Newgard, Mukesh K. Jain
Summary: Brown adipose tissue (BAT) is crucial for maintaining metabolic health and survival by regulating and utilizing nutrient resources. The transcription factor KLF15 plays a critical role in the metabolic flexibility of BAT.
Article
Multidisciplinary Sciences
Hillary Koch, Cheryl A. Keller, Guanjue Xiang, Belinda Giardine, Feipeng Zhang, Yicheng Wang, Ross C. Hardison, Qunhua Li
Summary: Comparing experimental results across multiple different conditions can be more precise and meaningful. Researchers have introduced a method called CLIMB that allows for this type of comparison and captures interpretable and biologically meaningful information.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Kunhua Qin, Xianjiang Lan, Peng Huang, Megan S. Saari, Eugene Khandros, Cheryl A. Keller, Belinda Giardine, Osheiza Abdulmalik, Junwei Shi, Ross C. Hardison, Gerd A. Blobel
Summary: BMI1, a subunit of PRC1, is identified as a novel repressor of fetal hemoglobin (HbF) and regulates this process through its target genes LIN28B, IGF2BP1, and IGF2BP3. PRC1 and PRC2 work together to repress HbF expression, revealing an epigenetic mechanism involved in hemoglobin switching.
Article
Cardiac & Cardiovascular Systems
David R. Sweet, Roshan Padmanabhan, Xudong Liao, Himanshu R. Dashora, Xinmiao Tang, Lalitha Nayak, Rajan Jain, Sarah De Val, Vinesh Vinayachandran, Mukesh K. Jain
Summary: This study investigates the transcriptional control mechanisms of KLF2 and KLF4 in heart and lung endothelium. The results show that KLF2 and KLF4 use open chromatin regions in promoters and enhancers, and bind context-specifically to govern transcription in microvasculature. This work provides insight into the transcriptional and functional heterogeneity seen in vascular populations, and establishes tools for exploring microvascular endothelial dynamics in vivo.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Biotechnology & Applied Microbiology
Jacob Schreiber, Carles Boix, Jin Wook Lee, Hongyang Li, Yuanfang Guan, Chun-Chieh Chang, Jen-Chien Chang, Alex Hawkins-Hooker, Bernhard Scholkopf, Gabriele Schweikert, Mateo Rojas Carulla, Arif Canakoglu, Francesco Guzzo, Luca Nanni, Marco Masseroli, Mark James Carman, Pietro Pinoli, Chenyang Hong, Kevin Y. Yip, Jeffrey P. Spence, Sanjit Singh Batra, Yun S. Song, Shaun Mahony, Zheng Zhang, Wuwei Tan, Yang Shen, Yuanfei Sun, Minyi Shi, Jessika Adrian, Richard Sandstrom, Nina Farrell, Jessica Halow, Kristen Lee, Lixia Jiang, Xinqiong Yang, Charles Epstein, J. Seth Strattan, Bradley Bernstein, Michael Snyder, Manolis Kellis, William Stafford, Anshul Kundaje
Summary: A promising alternative to conducting comprehensive genomics experiments is to perform a subset of experiments and use computational methods to impute the remaining data. However, determining the best imputation methods and meaningful performance evaluation measures remains an open question. In this study, we address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. Our findings indicate that imputation evaluations are challenging due to distributional shifts caused by differences in data collection and processing, the amount of available data, and redundancy among performance measures. Our analyses provide insights into overcoming these challenges and offer promising directions for more robust research.
Article
Biotechnology & Applied Microbiology
Danying Shao, Gretta D. Kellogg, Ali Nematbakhsh, Prashant K. Kuntala, Shaun Mahony, B. Franklin Pugh, William K. M. Lai
Summary: Reproducibility is a significant challenge in (epi)genomic research, especially with the rapid generation of high-throughput sequencing data. We have developed a web-based project management platform called PEGR that tracks and quality controls experiments, compatible with multiple assays and bioinformatic pipelines, supporting rigor and reproducibility for biochemists and bioinformaticians.
Article
Medicine, Research & Experimental
Xinmiao Tang, Peiwei Wang, Rongli Zhang, Ippei Watanabe, Eugene Chang, Vinesh Vinayachandran, Lalitha Nayak, Stephanie Lapping, Sarah Liao, Annmarie Madera, David R. Sweet, Jiemeng Luo, Jinsong Fei, Hyun-Woo Jeong, Ralf H. Adams, Teng Zhang, Xudong Liao, Mukesh K. Jain
Summary: The role of inflammation and inflammatory cells, particularly neutrophils, in cardiac hypertrophy and heart failure has been investigated in this study. It was found that neutrophils play a crucial role in the pathogenesis and progression of heart failure by triggering thrombosis in small myocardial vessels through the KLF2/NETosis pathway. Targeting neutrophils, NETosis, or thrombosis can alleviate pathological changes and preserve cardiac dysfunction.
JOURNAL OF CLINICAL INVESTIGATION
(2022)