Article
Biochemistry & Molecular Biology
Yaoguang Yu, Wei Fu, Jianqu Xu, Yawen Lei, Xin Song, Zhenwei Liang, Tao Zhu, Yuhui Liang, Yuanhao Hao, Liangbing Yuan, Chenlong Li
Summary: The Arabidopsis thaliana bromodomain-containing proteins BRD1, BRD2, and BRD13 are core subunits of SWI/SNF complexes and play critical roles in genomic targeting. These BRDs interact directly with multiple SWI/SNF subunits, including the BRAHMA (BRM) catalytic subunit, to control gene expression and developmental processes. The bromodomains of BRDs are essential for genomic targeting of SWI/SNF complexes.
Article
Developmental Biology
Doerthe Holdhof, Melanie Schoof, Sina Al-Kershi, Michael Spohn, Catena Kresbach, Carolin Goebel, Malte Hellwig, Daniela Indenbirken, Natalia Moreno, Kornelius Kerl, Ulrich Schueller
Summary: The loss of the Brg1 gene in neural stem cells results in abnormal brain and eye development, including morphological alterations, decreased cell survival rates, and impaired neuronal functions, suggesting a crucial role for Brg1 in central nervous system development.
Article
Gastroenterology & Hepatology
Yongjie Zhou, Yuwei Chen, Xiaoyun Zhang, Qing Xu, Zhenru Wu, Xiaoyue Cao, Mingyang Shao, Yuke Shu, Tao Lv, Changli Lu, Mingjun Xie, Tianfu Wen, Jiayin Yang, Yujun Shi, Hong Bu
Summary: The study demonstrates that Brg1 plays a key role in promoting HPC expansion, liver cirrhosis, and iCCA development, which is largely dependent on the Wnt/beta-catenin signaling pathway. Therapies targeting Brg1-expressing HPCs may hold promise for the treatment of liver cirrhosis and iCCA.
Article
Oncology
Theresa Bluemn, Jesse Schmitz, Yongwei Zheng, Robert Burns, Shikan Zheng, Joshua DeJong, Luke Christiansen, Olivia Arnold, Jesus Izaguirre-Carbonell, Demin Wang, Aniruddha J. Deshpande, Nan Zhu
Summary: The SWI/SNF nucleosome remodeling complexes have diverse roles in AML leukemogenesis, with Arid2 enhancing leukemia initiation but being required for leukemia maintenance, while the deletion of Arid1b promotes leukemogenesis at any stage.
Article
Genetics & Heredity
Christine A. Tabuloc, Yao D. Cai, Rosanna S. Kwok, Elizabeth C. Chan, Sergio Hidalgo, Joanna C. Chiu
Summary: The circadian clock and chromatin-remodeling complexes regulate rhythmic gene expression. BRM complex promotes the repression of circadian gene expression in Drosophila. Clock proteins CLK and TIM regulate BRM occupancy at clock gene promoters, with CLK enhancing BRM binding and TIM promoting BRM removal from DNA. Light also affects BRM binding to DNA. This study provides new insights into the reciprocal regulation between the circadian clock and the BRM chromatin-remodeling complex.
Article
Plant Sciences
Xiaowei Lin, Tingting Yuan, Hong Guo, Yi Guo, Nobutoshi Yamaguchi, Shuge Wang, Dongxia Zhang, Dongmei Qi, Jiayu Li, Qiang Chen, Xinye Liu, Long Zhao, Jun Xiao, Doris Wagner, Sujuan Cui, Hongtao Zhao
Summary: This study reveals that LFR is a subunit of the SYD-containing SWI/SNF complex in Arabidopsis, and LFR and SYD together regulate the transcription of the AG gene by controlling chromatin conformation and histone modifications at the AG locus.
Article
Pathology
Basile Tessier-Cloutier, Felix K. F. Kommoss, David L. Kolin, Kristyna Nemejcova, Dupreez Smith, Jennifer Pors, Colin J. R. Stewart, W. Glenn Mccluggage, William D. Foulkes, Andreas von Deimling, Martin Kobel, Cheng-Han Lee
Summary: This study provides a detailed analysis of the clinical, pathological, immunohistochemical, and molecular features of DDOC/UDOC. The majority of patients presented with extraovarian disease and had rapid disease progression resulting in high mortality rate.
Article
Oncology
Kai Zimmer, Florian Kocher, Gerold Untergasser, Brigitte Kircher, Arno Amann, Yasmine Baca, Joanne Xiu, W. Micheal Korn, Martin D. D. Berger, Heinz-Josef Lenz, Alberto Puccini, Elisa Fontana, Anthony F. F. Shields, John L. L. Marshall, Michael Hall, Wafik S. S. El-Deiry, David Hsiehchen, Teresa Macarulla, Josep Tabernero, Renate Pichler, Moh'd Khushman, Upender Manne, Emil Lou, Dominik Wolf, Viktorija Sokolova, Simon Schnaiter, Alain G. G. Zeimet, Pat Gulhati, Gerlig Widmann, Andreas Seeber
Summary: Loss of function mutations in the PBRM1 gene are found in a fraction of biliary tract cancers (BTCs) and may be involved in chromatin remodeling and DNA damage repair. Through analyzing 1848 samples, it was found that PBRM1 mutations occur in 8.1% of BTCs and are more common in intrahepatic BTCs. Furthermore, PBRM1 mutations are associated with higher co-mutation rates in other chromatin remodeling and DNA damage repair genes. In vitro experiments showed that PBRM1-deficient BTC models are sensitive to PARP and ATR inhibitors. These findings provide a theoretical basis for future treatment of BTC patients with PBRM1 mutations.
NPJ PRECISION ONCOLOGY
(2023)
Review
Genetics & Heredity
Liyuan Wang, Jinglong Tang
Summary: Epigenetics studies genetic changes that affect gene expression without altering DNA sequence, such as DNA methylation, histone modification, chromatin remodelling, X chromosome inactivation, and non-coding RNA regulation. DNA methylation, histone modification, and chromatin remodelling are the three classical modes of epigenetic regulation. Mutations in the SWI/SNF complex, one of the ATP-dependent chromatin remodelling complexes, are prevalent in various cancers and can impact tumorigenesis and cancer progression.
Review
Biochemistry & Molecular Biology
Ieva Vaicekauskaite, Rasa Sabaliauskaite, Juozas Rimantas Lazutka, Sonata Jarmalaite
Summary: Ovarian cancer is the fifth leading cause of women's death from cancers, with high mortality rate due to late presence and lack of modern diagnostic tools. It is a highly heterogeneous disease, leading to early treatment failure. Exploring molecular mechanisms of ovarian cancer can enhance our understanding and provide new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lena Wischhof, Hang-Mao Lee, Janine Tutas, Clemens Overkott, Eileen Tedt, Miriam Stork, Michael Peitz, Oliver Bruestle, Thomas Ulas, Kristian Haendler, Joachim L. Schultze, Dan Ehninger, Pierluigi Nicotera, Paolo Salomoni, Daniele Bano
Summary: Mammalian SWI/SNF/BAF chromatin remodeling complexes, particularly the modulator BCL7A, play crucial roles in regulating Notch/Wnt pathway signaling and mitochondrial bioenergetics during neuronal progenitor cell differentiation, ultimately affecting neuronal morphogenesis, cognitive flexibility, and behavioral performance.
Article
Plant Sciences
Raul Huertas, Ivone Torres-Jerez, Shaun J. Curtin, Wolf Scheible, Michael Udvardi
Summary: Three PHO2-like genes in Medicago truncatula were characterized for their potential roles in phosphorus and nitrogen metabolism balance and symbiotic nitrogen fixation. Among them, MtPHO2B may play a key role in the balance of phosphorus and nitrogen, while MtPHO2C has limited regulatory effects on phosphorus metabolism. Genetic analysis also revealed a connection between phosphorus allocation, plant growth, and symbiotic nitrogen fixation performance. In conclusion, MtPHO2 genes play important roles in both systemic and localized (nodules) phosphorus metabolism.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Multidisciplinary Sciences
Ao Guo, Hongling Huang, Zhexin Zhu, Mark J. Chen, Hao Shi, Sujing Yuan, Piyush Sharma, Jon P. Connelly, Swantje Liedmann, Yogesh Dhungana, Zhenrui Li, Dalia Haydar, Mao Yang, Helen Beere, Jason T. Yustein, Christopher DeRenzo, Shondra M. Pruett-Miller, Jeremy Chase Crawford, Giedre Krenciute, Charles W. M. Roberts, Hongbo Chi, Douglas R. Green
Summary: This study identifies components of the cBAF complex as negative regulators of T-mem cell generation and provides insights into the asymmetric distribution of cBAF and MYC during the division of activated CD8+ T cells. Manipulation of cBAF early in T cell differentiation has the potential to improve cancer immunotherapy, as demonstrated in a mouse solid tumor model.
Article
Biochemistry & Molecular Biology
Dan-Dan He, Xue-Ying Shang, Na Wang, Guang-Xing Wang, Kun-Yan He, Lan Wang, Ze-Guang Han
Summary: This study identifies a potential therapeutic strategy for HCC patients with ARID2 mutations by discovering that BRD4 inhibition induces synthetic lethality in ARID2-deficient HCC cells. JQ1, a selective inhibitor, is found to selectively suppress the growth of ARID2-deficient HCC cells by exacerbating DNA damage. Functional assays demonstrate that both BRD4 inhibition and ARID2 deficiency synergistically impede DNA damage repair pathways by attenuating the transcription of core molecules responsible for repair. This study provides insight into a potential therapeutic option for HCC patients with ARID2 mutations.
Article
Multidisciplinary Sciences
Dominik Laubscher, Berkley E. Gryder, Benjamin D. Sunkel, Thorkell Andresson, Marco Wachtel, Sudipto Das, Bernd Roschitzki, Witold Wolski, Xiaoli S. Wu, Hsien-Chao Chou, Young K. Song, Chaoyu Wang, Jun S. Wei, Meng Wang, Xinyu Wen, Quy Ai Ngo, Joana G. Marques, Christopher R. Vakoc, Beat W. Schafer, Benjamin Z. Stanton, Javed Khan
Summary: The study demonstrates that the BRG1-containing BAF complex is overexpressed in FP-RMS and acts independently on chromatin from the PAX3-FOXO1 chimera, resulting in a blockade of myogenic differentiation in this malignancy.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Maxime Parisotto, Elise Grelet, Rana El Bizri, Yongyuan Dai, Julie Terzic, Doriane Eckert, Laetitia Gargowitsch, Jean-Marc Bornert, Daniel Metzger
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Physiology
Julien Pottecher, Chris Adamopoulos, Anne Lejay, Jamal Bouitbir, Anne-Laure Charles, Alain Meyer, Mervyn Singer, Valerie Wolff, Pierre Diemunsch, Gilles Laverny, Daniel Metzger, Bernard Geny
FRONTIERS IN PHYSIOLOGY
(2018)
Editorial Material
Medicine, Research & Experimental
Elise Grelet, Maxime Parisotto, Daniel Metzger
M S-MEDECINE SCIENCES
(2018)
Article
Cardiac & Cardiovascular Systems
Hana E. Baker, Alexander M. Kiel, Samuel T. Luebbe, Blake R. Simon, Conner C. Earl, Ajit Regmi, William C. Roell, Kieren J. Mather, Johnathan D. Tune, Adam G. Goodwill
BASIC RESEARCH IN CARDIOLOGY
(2019)
Article
Endocrinology & Metabolism
Derek B. J. Bone, Jaroslawna Meister, Jonas R. Knudsen, Diptadip Dattaroy, Amanda Cohen, Regina Lee, Huiyan Lu, Daniel Metzger, Thomas E. Jensen, Jurgen Wess
Letter
Cardiac & Cardiovascular Systems
Hana E. Baker, Johnathan D. Tune, Adam G. Goodwill, Kieren J. Mather
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2019)
Review
Cardiac & Cardiovascular Systems
Johnathan D. Tune, Adam G. Goodwill, Alexander M. Kiel, Hana E. Baker, Shawn B. Bender, Daphne Merkus, Dirk J. Duncker
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2020)
Review
Cardiac & Cardiovascular Systems
Oana Sorop, Jens van de Wouw, Selena Chandler, Vahagn Ohanyan, Johnathan D. Tune, William M. Chilian, Daphne Merkus, Shawn B. Bender, Dirk J. Duncker
CARDIOVASCULAR RESEARCH
(2020)
Article
Multidisciplinary Sciences
Daniela Rovito, Anna Y. Belorusova, Sandra Chalhoub, Anna-Isavella Rerra, Elvire Guiot, Arnaud Molin, Agnes Linglart, Natacha Rochel, Gilles Laverny, Daniel Metzger
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Mohamed A. Abu el Maaty, Elise Grelet, Celine Keime, Anna-Isavella Rerra, Justine Gantzer, Camille Emprou, Julie Terzic, Regis Lutzing, Jean-Marc Bornert, Gilles Laverny, Daniel Metzger
Summary: The study found that Gemini-72 induced apoptosis in senescent prostatic intraepithelial neoplasia cells, normalized extracellular matrix remodeling by stromal fibroblasts, and reduced the infiltration of immunosuppressive myeloid-derived cells. Single-cell RNA-sequencing analysis showed that while a subset of luminal cells were lost after treatment, antiapoptotic pathways were induced in persistent luminal cells.
Article
Medicine, Research & Experimental
Julie Terzic, Mohamed A. Abu el Maaty, Regis Lutzing, Alexandre Vincent, Rana El Bizri, Matthieu Jung, Celine Keime, Daniel Metzger
Summary: Androgen deprivation therapy is a key treatment for prostate cancer, but some cases develop into castration-resistant prostate cancer (CRPC). In this study, it was found that the major luminal cell population in CRPC is castration-resistant, with enhanced expression of inflammation and stemness markers. Additionally, hypoxia-inducible factor 1 (HIF1) signaling, which promotes malignant progression, is further activated. Inhibition of HIF1A enhances the sensitivity of Pten-deficient prostatic tumors to castration and induces apoptotic signaling in human CRPC cell lines.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Anna Y. Belorusova, Daniela Rovito, Yassmine Chebaro, Stefanie Doms, Lieve Verlinden, Annemieke Verstuyf, Daniel Metzger, Natacha Rochel, Gilles Laverny
Summary: This study demonstrates that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs, restore the transcriptional activities of VDR variants unresponsive to the natural ligand. The elucidated mechanisms of action highlight the mutual adaptation between the ligand and the VDR ligand-binding pocket.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Katsuya Miyajima, Chiaki Kawamoto, Satoshi Hara, Masayo Mori-Kojima, Tamae Ohye, Chiho Sumi-Ichinose, Nae Saito, Toshikuni Sasaoka, Daniel Metzger, Hiroshi Ichinose
Summary: The study revealed that dopamine (DA) supply in peripheral organs originates from sympathetic neurons, with decreased TH protein and NA levels leading to a decrease in DA content in the heart and pancreas. TH-immunoreactive cells were found in the stomach and lung, showing a decreasing trend in TH protein levels but not in DA levels. Additionally, there was a significant correlation between DA content in the kidney and plasma DOPA concentration.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Stephanie Paradis, Anne-Laure Charles, Isabelle Georg, Fabienne Goupilleau, Alain Meyer, Michel Kindo, Gilles Laverny, Daniel Metzger, Bernard Geny
Article
Oncology
Maxime Parisotto, Elise Grelet, Rana El Bizri, Daniel Metzger
MOLECULAR & CELLULAR ONCOLOGY
(2019)