Article
Medicine, Research & Experimental
Maggie H. Chasse, Benjamin K. Johnson, Elissa A. Boguslawski, Katie M. Sorensen, Jessica E. Rosien, Min H. Kang, C. Patrick Reynolds, Lyong Heo, Zachary B. Madaj, Ian Beddows, Gabrielle E. Foxa, Susan M. Kitchen-Goosen, Bart O. Williams, Timothy J. Triche, Patrick J. Grohar
Summary: The study found that rhabdoid tumors are more sensitive to mithramycin and EC8042, with their sensitivity superior to traditional DNA damaging agents and linked to the causative mutation of SMARCB1 deletion in the tumor. Mithramycin can block the activity of SMARCB1-deficient SWI/SNF complex, leading to chromatin remodeling and restoration of cellular differentiation.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Carlos Jimenez, Roberta Antonelli, Mariona Nadal-Ribelles, Laura Devis-Jauregui, Pablo Latorre, Carme Sole, Marc Masanas, Adria Molero-Valenzuela, Aroa Soriano, Josep Sanchez de Toledo, David Llobet-Navas, Josep Roma, Francesc Posas, Eulalia de Nadal, Soledad Gallego, Lucas Moreno, Miguel F. Segura
Summary: Loss of function of mSWI/SNF complexes in neuroblastoma impairs cell proliferation and inhibits tumor invasion and metastasis. Disruption of the BAF complex results in epigenetic repression of invasion-related genes, significantly inhibiting neuroblastoma metastasis. These findings provide important insights for the development of new therapeutic strategies targeting mSWI/SNF complexes in neuroblastoma.
Article
Developmental Biology
Rodrigo O. de Castro, Luciana Previato de Almeida, Agustin Carbajal, Irma Gryniuk, Roberto J. Pezza
Summary: Gametogenesis in mammals involves regulated developmental transitions and changes in gene transcription. SWI/SNF chromatin remodelers are involved in gene transcription and DNA repair, but their role in meiosis is not well understood. Conditional knockout mice for ARID2, a regulatory subunit of PBAF, were generated and compared with BRG1 knockout mice. ARID2 activity is required at the end of prophase I, while BRG1 acts at an early stage of meiosis. Defects in spindle assembly and chromosome-spindle attachment in ARID2 knockout mice are attributed to an increase in aurora B kinase at centromeres. Different PBAF complexes regulate different stages of meiosis and gametogenesis.
Review
Chemistry, Medicinal
Karolina Pyziak, Agnieszka Sroka-Porada, Tomasz Rzymski, Jozef Dulak, Agnieszka Loboda
Summary: EZH2, a catalytic component of PRC2, is commonly overexpressed or mutated in various cancer types, with inhibitors currently in clinical trials. Synthetic lethality, especially targeting SWI/SNF complex, may provide alternative treatment approaches for cancers with aberrant EZH2 expression. Further research on EZH2 inhibitors and their application in cancers with SWI/SNF mutations is needed.
DRUG DEVELOPMENT RESEARCH
(2021)
Article
Cell Biology
Ziqing Yang, Dandan Huang, Manqi Meng, Wencong Wang, Junyan Feng, Lekun Fang, Honglei Chen, Shaomin Zou
Summary: BAF53A is upregulated in colorectal cancer (CRC) and promotes CRC cell proliferation, colony formation, and tumorigenesis. Furthermore, BAF53A also participates in the development of CRC by regulating the DUSP5-ERK1/2 pathway.
CELL DEATH & DISEASE
(2022)
Editorial Material
Cell Biology
Krystal A. Orlando, Paul A. Wade
Summary: FGFR-altered triple negative breast cancer develops adaptive resistance to FGFR inhibitor therapy, but a new study shows that dual inhibition of YAP or mTORC1 and FGFR has a synergistic effect on tumor growth. This indicates a potential new approach for treating this type of cancer.
NATURE CELL BIOLOGY
(2021)
Article
Plant Sciences
Xiaowei Lin, Can Yuan, Bonan Zhu, Tingting Yuan, Xiaorong Li, Shan Yuan, Sujuan Cui, Hongtao Zhao
Summary: This study reveals the interaction between the Leaf and Flower Related (LFR) protein and SWI3B component of the chromatin-remodeling complex, highlighting their role in regulating transcription factors and auxin metabolism enzymes during Arabidopsis leaf development. Inhibition of SWI3B resulted in a leaf phenotype similar to the loss-of-function mutants of LFR, indicating their collaborative function in leaf development. The findings demonstrate the importance of LFR-SWI3B interaction in influencing gene expression and leaf morphology.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Developmental Biology
Chunming Guo, Yingsheng Zhang, Ruirong Tan, Zonghao Tang, Christa M. Lam, Xing Ye, Zhong Wang, Xue Li
Summary: Epigenetic regulation, specifically through the ATPase-dependent chromatin remodeling mechanism, plays a central role in bladder urothelium development and maintenance. This study uncovers the functions of Arid1a, a subunit of the SWI/SNF or BAF chromatin remodeling ATPase complex, in both embryonic and adult bladder urothelium. Arid1a deletion leads to increased cell proliferation and ectopic cell proliferation in the bladder, and also antagonizes the PRC2-dependent epigenetic gene silencing program. These findings highlight the critical roles of Arid1a in urothelial development and regeneration.
DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Lisa Lampersberger, Francesca Conte, Subhanita Ghosh, Yutong Xiao, Jonathan Price, David Jordan, David Q. Matus, Peter Sarkies, Petra Beli, Eric A. Miska, Nicholas O. Burton
Summary: SWI/SNF complexes are important regulators of gene expression and development. This study identifies a specific mutation in the SWI/SNF subunit snfc-5 that prevents embryonic lethality in nematodes with a loss-of-function mutation in the subunit swsn-1. The study also reveals a potential therapeutic target for developmental disorders caused by mutations in SWI/SNF subunits.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Developmental Biology
Yu-Chun Tseng, Jennifer S. Crodian, Ryan Cabot
Summary: This study aims to determine the developmental requirements of two SWI/SNF subunits, SMARCB1 and BRD7, in porcine embryos. The findings indicate that knockdown of SMARCB1 dramatically reduces embryo developmental potential, while knockdown of BRD7 has a less severe impact. Furthermore, knockdown of SMARCB1 alters the expression of NANOG and POU5F1.
REPRODUCTION FERTILITY AND DEVELOPMENT
(2022)
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
Oncology
Paola Peinado, Alvaro Andrades, Marta Cuadros, Maria Isabel Rodriguez, Isabel F. Coira, Daniel J. Garcia, Maria S. Benitez-Cantos, Carlos Cano, Eduardo Zarzuela, Javier Munoz, Claudia Loidi, Monica Saiz, Pedro P. Medina
Summary: We used multiple -omics methods to assess SWI/SNF composition and aberrations in LUAD. Mutations in lung SWI/SNF subunits were highly recurrent and predicted to have functional impact. SWI/SNF expression in LUAD suffered overall repression and mutations were associated with poorer overall survival.
CLINICAL EPIGENETICS
(2022)
Review
Biochemistry & Molecular Biology
Yijiang Shi, Daniel Sanghoon Shin
Summary: Lung cancer is a major cause of death worldwide. Molecularly targeted therapeutics and immunotherapy have greatly improved the care of NSCLC patients. However, not all patients benefit from these treatments and reliable biomarkers for immunotherapy are lacking. Alterations of the SWI/SNF chromatin remodeler are common in NSCLC patients, leading to poor response to standard therapies. Different subunits of the SWI/SNF complex have unique impacts on tumorigenesis and treatment response. Further studies are needed to evaluate the impact of SWI/SNF alterations on immunotherapy response in NSCLC patients. Combining inhibitors of chromatin modulators with immunotherapy has shown effectiveness in treating NSCLC with SWI/SNF deficiencies.
Article
Biology
Jiyoon Beon, Sungwook Han, Hyeokjun Yang, Seung Eun Park, Kwangbeom Hyun, Song-Yi Lee, Hyun-Woo Rhee, Jeong Kon Seo, Jaehoon Kim, Seyun Kim, Daeyoup Lee
Summary: Inositol polyphosphate multikinase (IPMK) interacts with the chromatin remodeling complex SWI/SNF and regulates its function in mouse embryonic stem cells, contributing to transcription and differentiation.
Article
Oncology
Molly E. Heft Neal, Andrew C. Birkeland, Apurva D. Bhangale, Jingyi Zhai, Aditi Kulkarni, Susan K. Foltin, Brittany M. Jewell, Megan L. Ludwig, Lisa Pinatti, Hui Jiang, Jonathan B. McHugh, Lawence Marentette, Erin L. McKean, J. Chad Brenner
Summary: This study evaluated the survival outcomes of 46 SNUC patients and identified tobacco use as the only significant predictor of survival. Additionally, it confirmed previously published findings on IDH and SMARC family mutations and discovered novel recurrent aberrations in the JAK/STAT and PI3K pathways. The study also validated a novel PGAP3-SRPK1 gene fusion and showed its negative association with EGFR, E2F, and MYC signaling.
Article
Biochemistry & Molecular Biology
Hao Li, Han Dong, Beisi Xu, Qing-Ping Xiong, Cai-Tao Li, Wen-Qing Yang, Jing Li, Zhi-Xuan Huang, Qi-Yu Zeng, En-Duo Wang, Ru-Juan Liu
Summary: The previously uncharacterized tRNA-modifying enzyme hTrmt13 is found to regulate transcription in a dual mechanism, catalyzing tRNA 2'-O-methylation in the cytoplasm for translation regulation and binding DNA as a transcriptional co-activator in the nucleus for promoting cell migration. These dual functions are mutually exclusive and the expression of hTrmt13 is correlated with poor prognosis in cancer patients. This discovery provides a new perspective for epitranscriptomic regulation.
Article
Biology
Xiaokang Wang, Wojciech Rosikiewicz, Yurii Sedkov, Tanner Martinez, Baranda S. Hansen, Patrick Schreiner, Jesper Christensen, Beisi Xu, Shondra M. Pruett-Miller, Kristian Helin, Hans-Martin Herz
Summary: This study identifies PROSER1 as a regulator of TET2 O-GlcNAcylation and its role in DNA demethylation. PROSER1 mediates the interaction between OGT and TET2, promoting TET2 O-GlcNAcylation and protein stability. Furthermore, PROSER1 colocalizes with UTX, TET1/2, and OGT on many genomic elements, suggesting its involvement in regulating chromatin-associated proteins via OGT-mediated O-GlcNAcylation.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Anand G. Patel, Xiang Chen, Xin Huang, Michael R. Clay, Natalia Komorova, Matthew J. Krasin, Alberto Pappo, Heather Tillman, Brent A. Orr, Justina McEvoy, Brittney Gordon, Kaley Blankenship, Colleen Reilly, Xin Zhou, Jackie L. Norrie, Asa Karlstrom, Jiyang Yu, Dominik Wodarz, Elizabeth Stewart, Michael A. Dyer
Summary: Through single-cell and single nucleus RNA sequencing, the study found that rhabdomyosarcoma recapitulates the developmental hierarchy of embryonal myogenesis. Chemotherapy can eliminate the most proliferative component with features of myoblasts, and the immature paraxial mesoderm population expands after treatment. This paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors.
DEVELOPMENTAL CELL
(2022)
Article
Developmental Biology
Fuyun Bian, Marwa Daghsni, Fangfang Lu, Silvia Liu, Jeffrey M. Gross, Issam Aldiri
Summary: The transcription factor Vsx2 plays a critical role in retinal proliferation and bipolar cell differentiation. It binds to and transactivates its enhancer in association with Pax6. Vsx2 deletion in mice results in specific abnormalities in retinal proliferation and bipolar cell differentiation. Vsx2 occupies cis-regulatory elements nearby genes associated with photoreceptor differentiation and homeostasis in both mouse and human retina. It can also suppress Otx2-dependent activation of the Prdm1 enhancer. These findings provide important insights into the mechanisms of Vsx2 engagement with gene regulatory networks in retinal development.
Article
Oncology
Alexander R. Kovach, Kristianne M. Oristian, David G. Kirsch, Rex C. Bentley, Changde Cheng, Xiang Chen, Po-Han Chen, Jen-Tsan Ashley Chi, Corinne M. Linardic
Summary: HES1 is a protein associated with the development of FN-RMS, and inhibition of HES1 expression can suppress the growth of FN-RMS cells, indicating that HES1 may be a therapeutic target for FN-RMS.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Stephanie C. Wu, Ahhyun Kim, Yijun Gu, Daniel I. Martinez, Loredana Zocchi, Claire C. Chen, Jocelyne Lopez, Kelsey Salcido, Sarah Singh, Jie Wu, Ali Nael, Claudia A. Benavente
Summary: Loss-of-function mutations at the RB1 gene worsen clinical outcomes in osteosarcoma. The study has identified UHRF1 as an important downstream effector of the RB/E2F signaling pathway that promotes cell proliferation, migration, invasion, angiogenesis, and metastasis in osteosarcoma. UHRF1 overexpression suppresses AMPK activation and SEMA3E expression, leading to increased angiogenesis. Additionally, UHRF1 affects the expression of extracellular vesicles and their cargo, including uPA, contributing to migration and metastasis. Knocking out Uhrf1 in a mouse model shows decreased metastasis and improved survival in RB1 loss-associated osteosarcoma.
Article
Cell Biology
Jianqin Jiao, Michelle Curley, Flavia A. Graca, Maricela Robles-Murguia, Abbas Shirinifard, David Finkelstein, Beisi Xu, Yiping Fan, Fabio Demontis
Summary: Protein quality control is essential for healthy aging but dysregulated in age-related diseases. This study discovers that proteolytic enzymes distinct from the autophagy-lysosome and ubiquitin-proteasome systems are downregulated during skeletal muscle aging in Drosophila. The transcription factor Ptx1 is identified as a regulator of protease expression, and its knockdown counteracts the age-associated downregulation of protease expression and improves muscle protein quality control and lifespan.
Article
Biochemistry & Molecular Biology
Cheng Tian, Liyuan Li, Qingfei Pan, Beisi Xu, Yizhen Li, Li Fan, Anthony Brown, Michelle Morrison, Kaushik Dey, Jun J. Yang, Jiyang Yu, Evan S. Glazer, Liqin Zhu
Summary: Intrahepatic cholangiocarcinoma (iCCA) is characterized by highly desmoplastic stroma. Contact between tumor cells and peritumoral myofibroblasts (pMFs) initially suppresses tumor cell growth but promotes invasion and dissemination in the long term. Vascular cell adhesion molecule-1 (Vcam1) plays a significant role in this process by regulating epithelial-to-mesenchymal transition. Overall, this study reveals the spatiotemporal regulation of iCCA growth and dissemination by pMFs in a Vcam1-dependent manner.
Article
Multidisciplinary Sciences
Jennifer L. Kamens, Stephanie Nance, Cary Koss, Beisi Xu, Anitria Cotton, Jeannie W. Lam, Elizabeth A. R. Garfinkle, Pratima Nallagatla, Amelia M. R. Smith, Sharnise Mitchell, Jing Ma, Duane Currier, William C. Wright, Kanisha Kavdia, Vishwajeeth R. Pagala, Wonil Kim, LaShanale M. Wallace, Ji-Hoon Cho, Yiping Fan, Aman Seth, Nathaniel Twarog, John K. Choi, Esther A. Obeng, Mark E. Hatley, Monika L. Metzger, Hiroto Inaba, Sima Jeha, Jeffrey E. Rubnitz, Junmin Peng, Taosheng Chen, Anang A. Shelat, R. Kiplin Guy, Tanja A. Gruber
Summary: Proteasome inhibition is found to be effective in KMT2Ar infant acute lymphoblastic leukemia, leading to the depletion of histone modifications and downregulation of KMT2A gene expression signature. A cohort of relapsed/refractory KMT2Ar patients treated with this approach showed a high overall response rate. This innovative treatment approach is now being evaluated in a multi-institutional upfront trial for infants with newly diagnosed ALL.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Tomoyoshi Tamura, Changde Cheng, Wenan Chen, Louis T. Merriam, Humra Athar, Yaunghyun H. Kim, Reshmi Manandhar, Muhammad Dawood Amir Sheikh, Mayra Pinilla-Vera, Jack Varon, Peter C. Hou, Patrick R. Lawler, William M. Oldham, Raghu R. Seethala, Yohannes Tesfaigzi, Alexandra J. Weissman, Rebecca M. Baron, Fumito Ichinose, Katherine M. Berg, Erin A. Bohula, David A. Morrow, Xiang Chen, Edy Y. Kim
Summary: Most patients die from neurological injury after cardiac arrest (CA). The systemic inflammatory response after CA is associated with poor outcomes but is not well understood. This study examines the immune cell network induced by CA and identifies specific cell subpopulations and interactions that are associated with poor neurological outcomes.
Article
Multidisciplinary Sciences
Yurika Matsui, Mohamed Nadhir Djekidel, Katherine Lindsay, Parimal Samir, Nina Connolly, Gang Wu, Xiaoyang Yang, Yiping Fan, Beisi Xu, Jamy C. Peng
Summary: The study shows that SNIP1 is critical for the survival and differentiation of stem cells in the developing brain. It regulates PRC2 activities downstream of TGFb and NFkB, influencing cell fates. Understanding the role of SNIP1 in brain development can provide insights into cell survival and death during development.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jie Fang, Shivendra Singh, Changde Cheng, Sivaraman Natarajan, Heather Sheppard, Ahmed Abu-Zaid, Adam D. Durbin, Ha Won Lee, Qiong Wu, Jacob Steele, Jon P. Connelly, Hongjian Jin, Wenan Chen, Yiping Fan, Shondra M. Pruett-Miller, Jerold E. Rehg, Selene C. Koo, Teresa Santiago, Joseph Emmons, Stefano Cairo, Ruoning Wang, Evan S. Glazer, Andrew J. Murphy, Taosheng Chen, Andrew M. Davidoff, Carolina Armengol, John Easton, Xiang Chen, Jun Yang
Summary: A improved MYC-driven hepatoblastoma-like murine model is developed and characterized in this study, which recapitulates the pathological features of embryonal type of hepatoblastoma and shows transcriptomics resembling the high-risk gene signatures of the human disease. Single-cell RNA-sequencing and CRISPR-Cas9 screening are used to identify distinct subpopulations of hepatoblastoma cells and druggable targets shared with human hepatoblastoma. The study also reveals genetic modifiers of chemotherapy response and suggests a potential therapeutic strategy for human hepatoblastoma.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Changde Cheng, Wenan Chen, Hongjian Jin, Xiang Chen
Summary: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying cellular biology at an unprecedented resolution, enabling the characterization of cellular heterogeneity, identification of rare but significant cell types, and exploration of cell-cell communications and interactions. Its applications are broad, spanning both basic and clinical research domains.
Article
Oncology
Sara Hetzel, Alexandra L. Mattei, Helene Kretzmer, Chunxu Qu, Xiang Chen, Yiping Fan, Gang Wu, Kathryn G. Roberts, Selina Luger, Mark Litzow, Jacob Rowe, Elisabeth Paietta, Wendy Stock, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Charles G. Mullighan, Alexander Meissner
Summary: In acute lymphoblastic leukemia (ALL), unlike most cancers, there is a highly methylated genome with CpG island hypermethylation, particularly pronounced in T cell ALL. This hypermethylation is influenced by TET2 and DNMT3B, suggesting a non-canonical regulation of methylation in ALL.
Article
Oncology
Kirsten M. Dickerson, Chunxu Qu, Qingsong Gao, Ilaria Iacobucci, Zhaohui Gu, Hiroki Yoshihara, Emily A. Backhaus, Yunchao Chang, Laura J. Janke, Beisi Xu, Gang Wu, Evangelia K. Papachristou, Clive S. D'Santos, Kathryn G. Roberts, Charles G. Mullighan
Summary: ZNF384-rearranged fusion oncoproteins play a crucial role in hematopoiesis and leukemia development by promoting hematopoietic cell expansion and skewing the differentiation direction. The expression of ZNF384 FO can disrupt specific genes in hematopoietic stem cells, potentially leading to leukemia.
BLOOD CANCER DISCOVERY
(2022)