Article
Biochemistry & Molecular Biology
Louisa Hill, Markus Jaritz, Hiromi Tagoh, Karina Schindler, Daniela Kostanova-Poliakova, Qiong Sun, Tanja A. Schwickert, Martin Leeb, Meinrad Busslinger
Summary: This article investigates the role of PAIR elements in activating VH gene recombination in early B cells. It is found that PAIR4 and V8.7E function as a regulatory unit to activate distal VH gene recombination. The involvement of CTCF in PAIR4 regulation is crucial. Additionally, insertion of V8.8E is sufficient to activate VH gene recombination.
Article
Immunology
Amy L. Kenter, Corey T. Watson, Jan-Hendrik Spille
Summary: During development, B and T lymphocytes generate diverse antigen receptors which allow organisms to respond to a wide range of pathogens. Studies suggest that genetic polymorphisms in the immunoglobulin heavy chain locus may influence immune-repertoire formation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Noga Korenfeld, Maya Finkel, Nufar Buchshtab, Meirav Bar-Shimon, Meital Charni-Natan, Ido Goldstein
Summary: The study reveals that glucagon and glucocorticoids play a role in the transcriptional regulation of amino acid catabolism genes, and their synergistic effect can enhance gluconeogenesis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhuoyi Liang, Lijuan Zhao, Adam Yongxin Ye, Sherry G. Lin, Yiwen Zhang, Chunguang Guo, Hai-Qiang Dai, Zhaoqing Ba, Frederick W. Alt
Summary: Immunoglobulin heavy chain variable region exons are assembled in progenitor -B cells, with VH, D, and JH gene segments located in separate clusters. CTCF-binding elements (CBEs) in the IGCR1 element and 3' Igh-CBEs play a role in segregating different domains and impeding RAG scanning. Downregulation of WAPL in progenitor -B cells neutralizes CBEs and promotes VH-to-DJH rearrangements. The gradual WAPL downregulation mechanism and the reinforcement of CBEs contribute to ordered V(D)J recombination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Xuefei Zhang, Hye Suk Yoon, Aimee M. Chapdelaine-Williams, Nia Kyritsis, Frederick W. Alt
Summary: This study reveals the critical role of 3' IgH CBEs in regulating gene transcription and joining during CSR processes, especially in focusing transcriptional activities on upstream C-H locus targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Ophelie A. Martin, Morgane Thomas, Marie Marquet, Charlotte Bruzeau, Armand Garot, Mylene Brousse, Sebastien Bender, Claire Carrion, Jee Eun Choi, Bao Q. Vuong, Patricia J. Gearhart, Robert W. Maul, Sandrine Le Noir, Eric Pinaud
Summary: This study found that the scaffold/matrix attachment regions (5'- and 3'-MARs(E mu)) flanking the intronic core enhancer (cE mu) within the immunoglobulin heavy chain locus (IgH) are conserved in mice and humans, but their physiological role in somatic hypermutation (SHM) is still unclear. The results showed that deletion of MARs(E mu) led to an inverted substitution pattern in SHM, with a decrease upstream from cE mu and an increase downstream of it. This defect was not due to a direct transcription-coupled effect, but rather the consequence of a defect in base excision repair-associated unfaithful repair process. The study revealed an unexpected function of MARs(E mu) in limiting the error-prone repair machinery to the variable region of Ig gene loci.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Bo Tang, Rui Sun, Dejie Wang, Haoyue Sheng, Ting Wei, Liguo Wang, Jun Zhang, Thai H. Ho, Lu Yang, Qiang Wei, Haojie Huang
Summary: Both the gene repressor and activator functions of EZH2 are implicated in cancer progression, with the histone reader protein ZMYND8 playing a role in modulating EZH2 function and cell migration and invasion. Depletion of ZMYND8 enhances EZH2's Polycomb-dependent function in certain cancer cells and suppresses the FOXM1 transcription program.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Bujamin H. Vokshi, Guillaume Davidson, Nassim Tawanaie Pour Sedehi, Alexandra Helleux, Marc Rippinger, Alexandre R. Haller, Justine Gantzer, Jonathan Thouvenin, Philippe Baltzinger, Rachida Bouarich, Valeria Manriquez, Sakina Zaidi, Priya Rao, Pavlos Msaouel, Xiaoping Su, Herve Lang, Thibault Tricard, Veronique Lindner, Didier Surdez, Jean-Emmanuel Kurtz, Franck Bourdeaut, Nizar M. Tannir, Irwin Davidson, Gabriel G. Malouf
Summary: By integrating RMC omics data, the researchers found that ferroptosis resistance contributes to the transformation of renal thick ascending limb cells into different RMC cell states. The process involves the loss of renal epithelial transcription factors TFCP2L1, HOXB9, and MITF, and the gain of oncogenic programs associated with MYC and NFE2L2 and ferroptosis resistance. SMARCB1 re-expression can reverse this transcriptional switch, repressing oncogenic programs and ferroptosis resistance, leading to ferroptotic cell death. Ferroptosis resistance is linked to the survival of renal thick ascending limb cells in a high iron environment associated with sickle cell trait, which may explain why RMC is the only SMARCB1-deficient tumor arising from epithelial cells.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ophelie Deze, Delfina Ordanoska, Delphine Rossille, Emma Miglierina, Brice Laffleur, Michel Cogne
Summary: Ig genes have the unique ability to be reshaped in B lymphocytes after encountering specific antigens, resulting in improved affinity and antibody production. Ig class switching, an important change in this process, is mediated by DNA repeats and DNA lesions. The discovery of IgH-like DNA repeats in the human IgH locus suggests their regulatory role in antibody production.
Article
Genetics & Heredity
Rossella Cianci, Giorgio Mancino, Elena Galli, Eliseo Serone, Renato Massoud, Pietro D'Addabbo, Andrea Poscia, Alberto Borghetti, Ottavia Porzio, Riccardo Marmo, Giovanni Gambassi, Domenico Frezza
Summary: This study found that the concentrations of IgG subclasses decrease from IgG1 to IgG4 in both children and adults. The 3'RR1 enhancer hs1.2 alleles contribute to the control of IgG subclasses levels, but not IgE levels. This indicates that IgG and IgE are regulated by different mechanisms in humans.
Article
Biochemistry & Molecular Biology
Mingsen Li, Liqiong Zhu, Jiafeng Liu, Huaxing Huang, Huizhen Guo, Li Wang, Lingyu Li, Sijie Gu, Jieying Tan, Jing Zhong, Bowen Wang, Zhen Mao, Yong Fan, Chunqiao Liu, Jin Yuan, Hong Ouyang
Summary: The co-expression of FOXC1 and PAX6 in human corneal epithelium suggests a potential regulatory mechanism for corneal development. FOXC1 deficiency leads to activation of keratinization pathway and reprogramming of corneal epithelial cells, disrupting collagen metabolic process and interferon signaling pathways, ultimately linking to corneal ulceration.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Immunology
Iman Dalloul, Brice Laffleur, Zeinab Dalloul, Batoul Wehbi, Florence Jouan, Baptiste Brauge, Paco Derouault, Jeanne Moreau, Sven Kracker, Alain Fischer, Anne Durandy, Sandrine Le Noir, Michel Cogne
Summary: AID is a key regulator of immunoglobulin gene diversification in B-cells, but recent research has shown that under certain conditions, the absence of AID can also lead to gene diversification. The repair process in these cases involves an increased usage of microhomology-mediated repair.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Lorenzo Rinaldi, Gregory Fettweis, Sohyoung Kim, David A. Garcia, Saori Fujiwara, Thomas A. Johnson, Theophilus T. Tettey, Laurent Ozbun, Gianluca Pegoraro, Michele Puglia, Blagoy Blagoev, Arpita Upadhyaya, Diana A. Stavreva, Gordon L. Hager
Summary: This study reveals that the interaction between a transcription factor and the cohesin loader NIPBL regulates gene activity, and this mechanism is achieved by promoting loop extrusion and long-range gene regulation at the chromatin level. Additionally, it is discovered that patients with cohesin mutations exhibit a reduced response to glucocorticoids.
Article
Multidisciplinary Sciences
Amit K. Singh, Qingrong Chen, Cu Nguyen, Daoud Meerzaman, Dinah S. Singer
Summary: Cohesin plays a role in regulating alternative splicing by interacting with splicing factors and influencing splicing patterns. Mutations in cohesin are associated with distinct splicing patterns in acute myeloid leukemia, and cohesin interacts with another splicing regulator, BRD4, to generate unique splicing patterns. These findings provide insights into the role of cohesin in both normal and leukemic cells and its contribution to human disease.
Article
Oncology
Tingting Liu, Juan Wang, Hongbo Yang, Qiushi Jin, Xiaotao Wang, Yihao Fu, Yu Luan, Qixuan Wang, Mark W. Youngblood, Xinyan Lu, Lucia Casadei, Raphael Pollock, Feng Yue
Summary: This study provides a comprehensive molecular characterization of liposarcoma, including analysis of the entire genome, transcriptome, enhancer landscape, and three-dimensional genome structure. It identifies tumor-specific transcripts and regulatory elements, as well as novel mechanisms such as enhancer coamplification and hijacking that contribute to the upregulation of oncogenes. By combining multiple techniques, the study partially resolves complex structural variations and reconstructs the local genome and giant chromosomes. Overall, it offers a valuable resource for liposarcoma research and enhances our understanding of gene dysregulation in cancer through altered enhancers and three-dimensional genome organization.
Article
Oncology
Noah J. Mathis, Connor J. Doyle, Daniel B. Rosen, N. Ari Wijetunga, Max Vaynrub, Meredith Bartelstein, David M. Guttmann, Victoria S. Brennan, Yoshiya J. Yamada, Erin F. Gillespie, Divya Yerramilli, Jonathan T. Yang
Summary: The rate of local salvage therapy for patients with nonspine bone metastases is low, and patients of younger age, higher Karnofsky performance status, and lesions in the pelvis are at higher risk of retreatment.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Infectious Diseases
Henning Gruell, Jesper D. Gunst, Yehuda Z. Cohen, Marie H. Pahus, Jakob J. Malin, Martin Platten, Katrina G. Millard, Martin Tolstrup, R. Brad Jones, Winnifer D. Conce Alberto, Julio C. C. Lorenzi, Thiago Y. Oliveira, Tim Kuemmerle, Isabelle Suarez, Cecilia Unson-O'Brien, Lilian Nogueira, Rikke Olesen, Lars Ostergaard, Henrik Nielsen, Clara Lehmann, Michel C. Nussenzweig, Gerd Faetkenheuer, Florian Klein, Marina Caskey, Ole S. Sogaard
Summary: This study investigated the effect of combining the broadly neutralising antibody 3BNC117 with the latency-reversing agent romidepsin in people with HIV-1 on suppressive antiretroviral therapy (ART). The results showed that this combination therapy was safe but did not delay viral rebound during treatment interruptions in individuals on long-term ART.
Article
Immunology
Zijun Wang, Frauke Muecksch, Alice Cho, Christian Gaebler, Hans-Heinrich Hoffmann, Victor Ramos, Shuai Zong, Melissa Cipolla, Briana Johnson, Fabian Schmidt, Justin DaSilva, Eva Bednarski, Tarek Ben Tanfous, Raphael Raspe, Kaihui Yao, Yu E. Lee, Teresia Chen, Martina Turroja, Katrina G. Milard, Juan Dizon, Anna Kaczynska, Anna Gazumyan, Thiago Y. Oliveira, Charles M. Rice, Marina Caskey, Paul D. Bieniasz, Theodora Hatziioannou, Christopher O. Barnes, Michel C. Nussenzweig
Summary: SARS-CoV-2 infection or vaccination induces neutralizing antibody responses targeting the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike protein. This study identifies different groups of neutralizing antibodies, including some that can neutralize the Omicron variant. Structural analysis reveals the mechanism of action of broad neutralizers.
Article
Multidisciplinary Sciences
Christian Gaebler, Lilian Nogueira, Elina Stoffel, Thiago Y. Oliveira, Gaelle Breton, Katrina G. Millard, Martina Turroja, Allison Butler, Victor Ramos, Michael S. Seaman, Jacqueline D. Reeves, Christos J. Petroupoulos, Irina Shimeliovich, Anna Gazumyan, Caroline S. Jiang, Nikolaus Jilg, Johannes F. Scheid, Rajesh Gandhi, Bruce D. Walker, Michael C. Sneller, Anthony Fauci, Tae-Wook Chun, Marina Caskey, Michel C. Nussenzweig
Summary: Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells. A clinical study showed that 76% of HIV-infected individuals who received a combination of antibodies maintained virologic suppression for at least 20 weeks without antiretroviral therapy. The administration of antibodies affected the HIV-1 reservoir, but further research is needed to define the precise effect of antibody immunotherapy.
Article
Multidisciplinary Sciences
Frauke Muecksch, Zijun Wang, Alice Cho, Christian Gaebler, Tarek Ben Tanfous, Justin DaSilva, Eva Bednarski, Victor Ramos, Shuai Zong, Brianna Johnson, Raphael Raspe, Dennis Schaefer-Babajew, Irina Shimeliovich, Mridushi Daga, Kai-Hui Yao, Fabian Schmidt, Katrina G. Millard, Martina Turroja, Mila Jankovic, Thiago Y. Oliveira, Anna Gazumyan, Marina Caskey, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
Summary: Receiving three doses of an mRNA vaccine can provide protection against the Omicron variant and induce the production of more potent and broader antibodies. This is due to the expansion and evolution of memory B cell clones, particularly the newly emerging clones that target more conserved regions.
Article
Immunology
Alice Cho, Frauke Muecksch, Zijun Wang, Tarek Ben Tanfous, Justin DaSilva, Raphael Raspe, Brianna Johnson, Eva Bednarski, Victor Ramos, Dennis Schaefer-Babajew, Irina Shimeliovich, Juan P. Dizon, Kai-Hui Yao, Fabian Schmidt, Katrina G. Millard, Martina Turroja, Mila Jankovic, Thiago Y. Oliveira, Anna Gazumyan, Christian Gaebler, Marina Caskey, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
Summary: The article discusses the antibody immune response to the Ad26.COV2.S vaccine and mRNA vaccines after a single dose. It highlights that Ad26.COV2.S vaccination induces fewer memory B cells compared to mRNA vaccines, but the potency and breadth of the immune response are comparable. The Ad26.COV2.S vaccine also shows lower levels of neutralizing antibodies and limited efficacy against infection, especially during the Omicron surge.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Heathcliff Dorado Garcia, Fabian Pusch, Yi Bei, Jennifer von Stebut, Glorymar Ibanez, Kristina Guillan, Koshi Imami, Dennis Guergen, Jana Rolff, Konstantin Helmsauer, Stephanie Meyer-Liesener, Natalie Timme, Victor Bardinet, Rocio Chamorro Gonzalez, Ian C. MacArthur, Celine Y. Chen, Joachim Schulz, Antje M. Wengner, Christian Furth, Birgit Lala, Angelika Eggert, Georg Seifert, Patrick Hundsoerfer, Marieluise Kirchner, Philipp Mertins, Matthias Selbach, Andrej Lissat, Frank Dubois, David Horst, Johannes H. Schulte, Simone Spuler, Daoqi You, Filemon Dela Cruz, Andrew L. Kung, Kerstin Haase, Michela DiVirgilio, Monika Scheer, Michael V. Ortiz, Anton G. Henssen
Summary: This study demonstrates that PAX3-FOXO1-expressing alveolar rhabdomyosarcoma (ARMS) cells are sensitive to ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Inhibition of ATR leads to replication stress exacerbation and reduced DNA repair pathway activity, increasing the sensitivity of ARMS cells to PARP1 inhibition. Treatment with ATR and PARP1 inhibitors in combination induces complete regression of primary patient-derived ARMS xenografts, suggesting potential clinical applications. Additionally, the study identifies the RAS-MAPK pathway and FOS gene family as inducers of resistance to ATR inhibition in ARMS cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Thomas Hagglof, Melissa Cipolla, Maximilian Loewe, Spencer T. Chen, Luka Mesin, Harald Hartweger, Mohamed A. ElTanbouly, Alice Cho, Anna Gazumyan, Victor Ramos, Leonidas Stamatatos, Thiago Y. Oliveira, Michel C. Nussenzweig, Charlotte Viant
Summary: Antibody responses increase in both affinity and diversity over time, with affinity maturation occurring in germinal centers through somatic mutation and selection. The process of diversification while undergoing affinity maturation is not well understood.
Article
Biochemistry & Molecular Biology
Joanna Schneider, Devakumar Sundaravinayagam, Alexander Blume, Andreas Marg, Stefanie Grunwald, Eric Metzler, Helena Escobar, Stefanie Muethel, Haicui Wang, Tobias Wollersheim, Steffen Weber-Carstens, Altuna Akalin, Michela Di Virgilio, Baris Tursun, Simone Spuler
Summary: Critical illness myopathy (CIM) is a devastating muscle-wasting disease that has a significant impact on healthcare costs and quality of life. Impairment of muscle stem cells (MuSC) and epigenetic alterations may contribute to the incomplete recovery observed in CIM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Spencer T. Chen, Thiago Y. Oliveira, Anna Gazumyan, Melissa Cipolla, Michel C. Nussenzweig
Summary: Germinal centers (GCs) are crucial for the selection of high-affinity antibodies. The study found that B cell receptor (BCR) signaling plays a vital role in GC selection. These findings are fundamental for understanding adaptive immunity and vaccine development.
Article
Immunology
Harry B. Gristick, Harald Hartweger, Maximilian Loewe, Jelle van Schooten, Victor Ramos, Thiago Y. Oliveira, Yoshiaki Nishimura, Nicholas S. Koranda, Abigail Wall, Kai -Hui Yao, Daniel Poston, Anna Gazumyan, Marie Wiatr, Marcel Horning, Jennifer R. Keeffe, Magnus A. G. Hoffmann, Zhi Yang, Morgan E. Abernathy, Kim-Marie A. Dam, Han Gao, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Ana Jimena Pavlovitch-Bedzyk, Michael S. Seaman, Mark Howarth, Andrew T. Mcguire, Leonidas Stamatatos, Malcolm A. Martin, Anthony P. West Jr, Michel C. Nussenzweig, Pamela J. Bjorkman
Summary: Passive transfer of broadly neutralizing anti-HIV-1 antibodies is a strategy to protect against infection, but eliciting these antibodies through vaccination has been challenging. Researchers have successfully induced CD4 binding site (CD4bs) antibody responses using the antibody IOMA, which has potential as a vaccine strategy to generate broadly neutralizing antibodies against HIV-1.
SCIENCE IMMUNOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Martin T. King, Christopher E. Kehayias, Tafadzwa Chaunzwa, Daniel B. Rosen, Amandeep R. Mahal, Tyler D. Wallburn, Michael G. Milligan, M. Aiven Dyer, Paul L. Nguyen, Peter F. Orio, Thomas C. Harris, Ivan Buzurovic, Christian V. Guthier
Summary: This study evaluated the geometric accuracy and observer preference of an artificial intelligence algorithm for generating prostate contours on trans-rectal ultrasound (TRUS) images with implanted needles. The results showed that the algorithm provided high-quality prostate contours and was preferred by observers. Further research is needed to determine how to incorporate these AI prostate contours into the workflow of TRUS-based high dose rate brachytherapy.
Review
Immunology
Eleni Kabrani, Tannishtha Saha, Michela Di Virgilio
Summary: The repair factor 53BP1 has been long suggested to play a role in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, limited studies and diverse phenotypes associated with 53BP1 deficiency have hindered our understanding of its molecular activities. Recent findings on the downstream effectors of 53BP1 in DNA break protection and advances in genome architecture have led us to propose that in addition to end protection, 53BP1-mediated end-tethering stabilization is crucial for CSR. Furthermore, we support a role for 53BP1 before DNA breaks in V(D)J recombination. Our perspective highlights the importance of considering the dynamic architectural contexts in evaluating DNA break repair.
TRENDS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks, Michel C. Nussenzweig
Summary: Most proviruses in people living with HIV are defective, but intact proviruses can lead to viral rebound. The two-probe intact proviral DNA assay (IPDA) found 40-fold more intact proviruses compared to the near full length (nfl) Q4PCR. Both assays showed that defective proviruses did not decay over 10 years. However, the average half-lives of intact proviruses were different: 108 months for IPDA and 65 months for Q4PCR. Misclassified defective proviruses and very long-lived intact proviruses could explain this difference.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Julia Merkenschlager, Riza-Maria Berz, Victor Ramos, Maximilian Uhlig, Andrew J. Maclean, Carla R. Nowosad, Thiago Y. Oliveira, Michel C. Nussenzweig
Summary: This study found that follicular helper and regulatory T cells are continuously recruited into germinal centers during the germinal center reaction, and they quantitatively contribute to the remodeling of germinal centers.
NATURE COMMUNICATIONS
(2023)
