Article
Biochemistry & Molecular Biology
Tom Aharon Hait, Ran Elkon, Ron Shamir
Summary: In this study, we introduce the CT-FOCS method, which uses linear mixed effect models to infer enhancer-promoter links that are specifically active in certain cell types. The results show that CT-FOCS accurately predicts these links compared to other methods, and it reveals that strictly cell type-specific EP links are rare in the human genome.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Fabian Poetz, Joshua Corbo, Yevgen Levdansky, Alexander Spiegelhalter, Doris Lindner, Vera Magg, Svetlana Lebedeva, Jorg Schweiggert, Johanna Schott, Eugene Valkov, Georg Stoecklin
Summary: The study identified RNF219 as an acetylation-regulated cofactor of the CCR4-NOT complex, which inhibits mRNA degradation mediated by the complex through interaction with NOT9. RNF219 attenuates global mRNA turnover in cells with a differential requirement of its RING domain.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ying Huang, Jing An, Sanchari Sircar, Clara Bergis, Chloe Dias Lopes, Xiaoning He, Barbara Da Costa, Feng-Quan Tan, Jeremie Bazin, Javier Antunez-Sanchez, Maria Florencia Mammarella, Ravi-sureshbhai Devani, Rim Brik-Chaouche, Abdelhafid Bendahmane, Florian Frugier, Chongjing Xia, Christophe Rothan, Aline V. Probst, Zouine Mohamed, Catherine Bergounioux, Marianne Delarue, Yijing Zhang, Shaojian Zheng, Martin Crespi, Sotirios Fragkostefanakis, Magdy M. Mahfouz, Federico Ariel, Jose Gutierrez-Marcos, Cecile Raynaud, David Latrasse, Moussa Benhamed
Summary: This study examines the changes in chromatin and gene expression in response to heat stress in tomato. They found that heat stress rapidly alters chromatin structure and leads to the formation of temporary contacts between promoters and enhancers, which drive the expression of genes responsive to heat stress. The researchers also discovered that this spatial reorganization of chromatin requires the transcription factor HSFA1a.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Weizhi Ouyang, Xiwen Zhang, Minrong Guo, Jing Wang, Xiaoting Wang, Runxin Gao, Xu Xiang, Shiping Luan, Feng Xing, Zhilin Cao, Meng Ma, Jiapei Yan, Guoliang Li, Xingwang Li
Summary: In this study, high-resolution 3D genome maps were constructed using long-read chromatin interaction analysis, and the H3K27me3-associated chromatin interactions in an elite rice hybrid, Shanyou 63, were characterized. It was found that many H3K27me3-marked regions may function as silencer-like regulatory elements and can come into proximity with distal target genes via forming chromatin loops in the nuclei's 3D space. Additionally, genetic variations were identified to alter allelic chromatin topology and modulate allelic gene imprinting in rice hybrids.
Article
Biochemistry & Molecular Biology
Jie Dong, Chantal LeBlanc, Axel Poulet, Benoit Mermaz, Gonzalo Villarino, Kimberly M. Webb, Valentin Joly, Josefina Mendez, Philipp Voigt, Yannick Jacob
Summary: This study unveils a key molecular role for H3.1K27me1 in maintaining transcriptional silencing and genome stability in plants, by restricting GCN5-mediated histone acetylation. The findings also suggest that H3.1K27 and H3.1K36 play essential functions in inducing genomic instability in the absence of H3.1K27me1. Furthermore, H3.1K36 acetylation by GCN5 is negatively regulated by H3.1K27me1 in vitro.
Article
Cell Biology
Yujue Chen, Qian Zhang, Zhen Teng, Hong Liu
Summary: Centromeric transcription is crucial for maintaining centromeric cohesion, and manipulating centromeric transcription levels can regulate the cohesion of centromeres in human cells.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Immunology
Wanlin Cui, Yuji Nagano, Satoru Morita, Takeshi Tanoue, Hidehiro Yamane, Keiko Ishikawa, Toshiro Sato, Masato Kubo, Shohei Hori, Tadatsugu Taniguchi, Masanori Hatakeyama, Koji Atarashi, Kenya Honda
Summary: A novel ILC2 subset that constitutively expresses IL-4 was identified in the mouse intestine. The absence of gut microbiota had marginal effects, but feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4(+) ILC2s.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Andrea J. Kriz, David Colognori, Hongjae Sunwoo, Behnam Nabet, Jeannie T. Lee
Summary: The balance of cohesin eviction and retention plays a crucial role in regulating chromosomal structure, gene silencing, and inter-chromosomal interactions. Cohesin loss disrupts the superstructure of the Xi chromosome, while forced cohesin retention compromises spreading of RNA-Polycomb complexes and attenuates Xi silencing.
Article
Biology
Kendall E. Martin, Padmapriyadarshini Ravisankar, Manu Beerens, Calum A. MacRae, Joshua S. Waxman
Summary: This study reveals that the zebrafish transcription factor Nr2f1a prevents the progressive acquisition of ventricular and pacemaker cardiomyocyte identities within distinct regions of the atrium by maintaining the expression of nkx2.5. The findings provide insights into the molecular etiology of congenital heart defects and associated arrhythmias.
Article
Biochemistry & Molecular Biology
Shue Chen, Leah F. Rosin, Gianluca Pegoraro, Nellie Moshkovich, Patrick J. Murphy, Guoyun Yu, Elissa P. Lei
Summary: NURF301 is identified as a novel regulator of gypsy insulator body localization, promoting insulator barrier activity. It physically interacts with insulator proteins and co-localizes with them genome-wide. NURF301 functions through nucleosome repositioning and promoting 3D contact between insulator bodies and DNA binding sites.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Ying Lu, Yangyang Li, Qi Liu, Na Tian, Peng Du, Fangming Zhu, Yichao Han, Xinnan Liu, Xisheng Liu, Xiao Peng, Xiaoxia Wang, Yuchen Wu, Lingfeng Tong, Yakui Li, Yemin Zhu, Lifang Wu, Ping Zhang, Ye Xu, Hanbei Chen, Bin Li, Xuemei Tong
Summary: In colorectal cancer, intratumoral regulatory T cells (Tregs) exhibit low activity of the MondoA-thioredoxin-interacting protein (TXNIP) axis and increased glucose uptake. While MondoA-deficient Tregs promoted Th1 responses in a subcutaneous colorectal cancer model, Treg-specific MondoA knockout mice were more susceptible to colorectal cancer induction.
Article
Biochemical Research Methods
Weibing Wang, Lin Gao, Yusen Ye, Yong Gao
Summary: The study proposes a two-stage random forest-based machine learning method, CTCF-mediated Chromatin Interaction Prediction (CCIP), to predict CTCF-mediated chromatin loops. Experimental results demonstrate that the method predicts CTCF-mediated loops more accurately than other methods and that transitivity, when used as a properly defined attribute, is informative for predicting CTCF loops. This work contributes to the understanding of the formation mechanism and function of CTCF-mediated chromatin loops.
Article
Cell Biology
Binbin Xue, Huiyi Li, Shun Liu, Qing Feng, Yan Xu, Rilin Deng, Shengwen Chen, Jingjing Wang, Xinran Li, Mengyu Wan, Songqing Tang, Haizhen Zhu
Summary: This study reveals the crucial role of methionine oxidation in immune function, particularly in the activation of STAT2. The interference of methionine oxidation on STAT2 activation can be prevented by IFN treatment through the recruitment of methionine sulfoxide reductase MSRB2, which is enhanced by NAT9. The findings may provide insights into the clinical applications of IFN in immune-related diseases.
Article
Biotechnology & Applied Microbiology
Limiao Chen, Hongli Yang, Yisheng Fang, Wei Guo, Haifeng Chen, Xiaojuan Zhang, Wenjun Dai, Shuilian Chen, Qingnan Hao, Songli Yuan, Chanjuan Zhang, Yi Huang, Zhihui Shan, Zhonglu Yang, Dezhen Qiu, Xiaorong Liu, Lam-Son Phan Tran, Xinan Zhou, Dong Cao
Summary: This study identified the roles of the dehydration-inducible GmMYB14 gene in regulating plant architecture, high-density yield, and drought tolerance through the brassinosteroid pathway in soybean.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Review
Microbiology
Akira Ishihama, Tomohiro Shimada
Summary: This review summarizes the regulatory targets of more than 150 transcription factors from E. coli K-12, which can be classified into four families: nucleoid-associated bifunctional TFs, global regulators, local regulators, and single-target regulators. The nucleoid-associated TFs H-NS and StpA together play a silencing role for a set of non-essential genes, with LeuO and other global regulators indicated for anti-silencing.Overall, the hierarchy of TF network is proposed as a key framework of the bacterial genome regulation.
FEMS MICROBIOLOGY REVIEWS
(2021)
Article
Cell Biology
Elise Clayer, Daniel Frank, Holly Anderton, Shengbo Zhang, Andrew Kueh, Valentin Heim, Stephen L. Nutt, Michael Chopin, Philippe Bouillet
Summary: The role of CCCH-containing RNA-binding proteins in regulating inflammation is important. ZC3H12C is identified as a potential post-transcriptional regulator of tumor necrosis factor expression. ZC3H12C depletion in dendritic cells causes lymphadenopathy, but it does not significantly impact skin inflammation.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yunshun Chen, Bhupinder Pal, Geoffrey J. Lindeman, Jane E. Visvader, Gordon K. Smyth
Summary: This article extends our understanding of the development mechanism of breast cancer by providing quality control thresholds, processed data objects, complete cell annotation, and R code for analysis of a large-scale single-cell RNA expression atlas.
Article
Immunology
Charis E. Teh, Simon P. Preston, Alissa K. Robbins, Michael D. Stutz, James Cooney, Michelle P. Clark, Antonia N. Policheni, Cody C. Allison, Liana Mackiewicz, Philip Arandjelovic, Gregor Ebert, Marcel Doerflinger, Tania Tan, Lucille C. Rankin, Peggy P. Teh, Gabrielle T. Belz, Axel Kallies, Andreas Strasser, Marc Pellegrini, Daniel H. D. Gray
Summary: Targeting the immunosuppressive properties of FOXP3(+) regulatory T cells has therapeutic potential for treating autoimmune and inflammatory diseases. This study identifies caspase-8 as a central regulator of T-reg homeostasis, playing a context-specific role during immune responses. Inhibition of caspase-8 leads to accumulation of resistant effector T-regs, while inflammation induces necroptosis of caspase-8-deficient T-regs, enhancing immunity but increasing the risk of lethal inflammation. Additionally, human T-regs exhibit heightened sensitivity to necroptosis compared to conventional T cells.
SCIENCE IMMUNOLOGY
(2022)
Article
Hematology
Rachel Thijssen, Luyi Tian, Mary Ann Anderson, Christoffer Flensburg, Andrew Jarratt, Alexandra L. Garnham, Jafar S. Jabbari, Hongke Peng, Thomas E. Lew, Charis E. Teh, Quentin Gouil, Angela Georgiou, Tania Tan, Tirta M. Djajawi, Constantine S. Tam, John F. Seymour, Piers Blombery, Daniel H. D. Gray, Ian J. Majewski, Matthew E. Ritchie, Andrew W. Roberts, David C. S. Huang
Summary: Researchers used single-cell RNA sequencing to uncover the genetic and epigenetic changes associated with acquired resistance to Venetoclax in chronic lymphocytic leukemia (CLL). They found that these changes involve alterations in the BCL2 family of apoptosis regulators, particularly upregulation of the MCL1 gene and activation of NF-kappa B. MCL1 was identified as a direct transcriptional target of NF-kappa B. These findings highlight the plasticity of CLL cells in evading Venetoclax-induced apoptosis and provide insights for overcoming Venetoclax resistance.
Article
Medicine, Research & Experimental
Hema Preethi Subas Satish, Kathleen Zeglinski, Rachel T. Uren, Stephen L. Nutt, Matthew E. Ritchie, Quentin Gouil, Ruth M. Kluck
Summary: Despite their common use in research, monoclonal antibodies are not systematically sequenced. Researchers developed a three-day, cost-effective workflow called NAb-seq using long-read ONT sequencing to characterize monoclonal antibody genes from hybridoma cell lines and single cells. This method shows high accuracy, reliability, and scalability compared to traditional Sanger sequencing.
Article
Cell Biology
Johannes Wichmann, Catherine Pitt, Samantha Eccles, Alexandra L. Garnham, Connie S. N. Li-Wai-Suen, Rose May, Elizabeth Allan, Stephen Wilcox, Marco J. Herold, Gordon K. Smyth, Brendon J. Monahan, Tim Thomas, Anne K. Voss
Summary: Histone acetylation is crucial for chromatin conformation and gene transcription, and TIP60 is a key enzyme involved in this process. Loss of TIP60 leads to cell growth arrest and abnormal chromosome alignment during mitosis. However, cell survival is not affected. TIP60 is essential for the acetylation of H2AZ at lysine 7 and plays a role in the activation of transcription for thousands of genes, including those involved in metabolism.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Ashleigh R. Poh, Christopher G. Love, David Chisanga, James H. Steer, David Baloyan, Michael Chopin, Stephen Nutt, Jai Rautela, Nicholas D. Huntington, Nima Etemadi, Megan O'Brien, Ryan O'Keefe, Lesley G. Ellies, Christophe Macri, Justine D. Mintern, Lachlan Whitehead, Gangadhara Gangadhara, Louis Boon, Ashwini L. Chand, Clifford A. Lowell, Wei Shi, Fiona J. Pixley, Matthias Ernst
Summary: Genetic ablation or therapeutic inhibition of the myeloid-specific hematopoietic cell kinase (HCK) enhances the response to immunotherapy by modifying the tumor microenvironment and promoting immune cell activation.
Editorial Material
Immunology
Julie Tellier, Stephen L. Nutt
Article
Cell Biology
Wing Fuk Chan, Hannah D. Coughlan, Michelle Ruhle, Nadia Iannarella, Carolina Alvarado, Joanna R. Groom, Christine R. Keenan, Andrew J. Kueh, Adam K. Wheatley, Gordon K. Smyth, Rhys S. Allan, Timothy M. Johanson
Summary: The transcription factor Myc is tightly regulated by the use of distal regulatory enhancers. In this study, a previously unidentified enhancer of Myc was discovered in activated B cells. However, genetic deletion of this enhancer had limited impact on Myc expression and cell proliferation. The findings highlight the complexity and dynamics of the regulation of critical genes like Myc.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Hematology
Charis E. Teh, Hongke Peng, Meng-Xiao Luo, Tania Tan, Marie Trussart, Lauren J. Howson, Chong Chyn Chua, Christine Muttiah, Fiona Brown, Matthew E. Ritchie, Andrew H. Wei, Andrew W. Roberts, Vanessa L. Bryant, Mary Ann Anderson, Geoffrey J. Lindeman, David C. S. Huang, Rachel Thijssen, Daniel H. D. Gray
Summary: Venetoclax is effective for certain blood cancers, but relapse is common. Combining it with immunotherapies is promising, but its impact on normal immune cells is unclear. This study found minimal impact on T and NK cells, supporting the potential combination of Venetoclax with immunotherapies for better anti-tumor responses.
Article
Oncology
Clare E. Weeden, Velimir Gayevskiy, Claire Marceaux, Daniel Batey, Tania Tan, Kenta Yokote, Nina Tubau Ribera, Allison Clatch, Susan Christo, Charis E. Teh, Andrew J. Mitchell, Marie Trussart, Lucille C. Rankin, Andreas Obers, Jackson A. McDonald, Kate D. Sutherland, Varun J. Sharma, Graham Starkey, Rohit D'Costa, Phillip Antippa, Tracy Leong, Daniel Steinfort, Louis Irviing, Charles Swanton, Claire L. Gordon, Laura K. Mackay, Terence P. Speed, Daniel H. D. Gray, Marie-Liesse Asselin-Labat
Summary: Tissue-resident memory T (TRM) cells play a crucial role in local immune defense against infection and cancer progression. This study shows that chronic inflammation affects TRM activation and TRM cells present in tissues prior to tumor onset impact cancer evolution. In preclinical models, pre-existing TRM-like cells enhance immune cell recruitment, leading to tumor immune evasion and resistance to immune checkpoint inhibitors. These findings highlight the importance of TRM-like activity in shaping tumor immunogenicity and influencing immunotherapy outcomes.
Article
Immunology
Hesham D. D. Abdulla, Raed Alserihi, Christoffer Flensburg, Waruni Abeysekera, Meng-Xiao Luo, Daniel H. D. Gray, Xiaodong Liu, Gordon K. K. Smyth, Warren S. S. Alexander, Ian J. J. Majewski, Matthew P. P. McCormack
Summary: Abdulla et al. demonstrate that the LMO2 transcription factor promotes the development of T-lymphoblastic leukemia by inhibiting thymocyte competition in a transgenic mouse model.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemical Research Methods
Mengbo Li, Gordon K. Smyth
Summary: Mass spectrometry proteomics in biomedical research suffers from the problem of missing values in peptides. Many analysis strategies have been proposed to distinguish different types of missing values and estimate detection probabilities. A logit-linear function is used to accurately model the detection probability, showing that missing values are related to peptide intensity. A probability model is developed to infer the distribution of unobserved intensities from observed values.
Article
Biochemistry & Molecular Biology
Pedro L. Baldoni, Yunshun Chen, Soroor Hediyeh-zadeh, Yang Liao, Xueyi Dong, Matthew E. Ritchie, Wei Shi, Gordon K. Smyth
Summary: Differential expression analysis of RNA-seq is commonly used in bioinformatics. However, transcript-level quantifications are more uncertain due to the ambiguity of sequence reads. To address this issue, a new method is proposed to estimate the overdispersion caused by read-to-transcript ambiguity and generate scaled transcript counts, which improves the efficiency and accuracy of differential analysis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Shengbo Zhang, Jai Rautela, Naiara G. Bediaga, Tatiana B. Kolesnik, Yue You, Junli Nie, Laura F. Dagley, Justin Bedo, Hanqing Wang, Li Sun, Robyn Sutherland, Elliot Surgenor, Nadia Iannarella, Rhys Allan, Fernando Souza-Fonseca-Guimaraes, Yi Xie, Qike Wang, Yuxia Zhang, Yuekang Xu, Stephen L. Nutt, Andrew M. Lew, Nicholas D. Huntington, Sandra E. Nicholson, Michael Chopin, Yifan Zhan
Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)