Article
Oncology
Carlotta Zampieri, Emanuele Panatta, Vincenzo Corbo, Alessandro Mauriello, Gerry Melino, Ivano Amelio
Summary: This study reveals the molecular mechanism of drug-tolerant phenotype caused by p53 mutants in pancreatic cancer. Mutant p53 fine-tunes chromatin accessibility and orchestrates transcriptional activity, influencing the phenotypic evolution of pancreatic cancer, and strongly correlates with drug response and aggressive phenotype.
MOLECULAR ONCOLOGY
(2022)
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
Multidisciplinary Sciences
Jeffrey J. Moffat, Eui-Man Jung, Minhan Ka, Byeong Tak Jeon, Hyunkyoung Lee, Woo-Yang Kim
Summary: Investigating the neural function of the ARID1B gene revealed its essential role in neural progenitor proliferation and survival, impacting neurodevelopment and cognitive function. Conditional homozygous deletion of ARID1B in ventral neural progenitors led to ID- and ASD-like behaviors in mice, while deletion in cortical neural progenitors resulted in minor cognitive deficits.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Amir Momeni-Boroujeni, Chad Vanderbilt, Elham Youse, Nadeem R. Abu-Rustum, Carol Aghajanian, Robert A. Soslow, Lora H. Ellenson, Britta Weigelt, Rajmohan Murali
Summary: This study investigated the prevalence and clinicopathological associations of chromatin remodeling gene (CRG) alterations in endometrial carcinoma (EC). The results showed that about 66.4% of EC patients had CRG alterations, with ARID1A being the most commonly altered gene. These CRG alterations were associated with the clinicopathological features of EC and likely played a crucial role in its development.
GYNECOLOGIC ONCOLOGY
(2023)
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
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
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
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
Genetics & Heredity
Yuan Tian, Rachel K. Smith-Bolton
Summary: Chromatin modifiers are crucial for controlling gene expression during tissue regeneration in fruit fly larvae. Two SWI/SNF chromatin-remodeling complexes, PBAP and BAP, play distinct roles in regulating regenerative growth and developmental timing, as well as cell fate and patterning during the regeneration process.
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)
Review
Oncology
Motoyuki Tsuda, Akihisa Fukuda, Munenori Kawai, Osamu Araki, Hiroshi Seno
Summary: ATP-dependent chromatin remodeling complexes, particularly the SWI/SNF complex, play crucial roles in regulating gene expression and have been found to be mutated in a significant percentage of human cancers, including pancreatic ductal adenocarcinoma (PDA). Research has shown that the subunits of the SWI/SNF complex in PDA have context-dependent roles in tumorigenesis, with potential therapeutic implications for targeting their oncogenic or tumor-suppressive properties in PDA. Further understanding of the precise roles of SWI/SNF complex subunits in PDA is necessary for the development of novel therapeutic strategies against this lethal type of cancer.
Article
Oncology
Masayuki Hagiwara, Yota Yasumizu, Nami Yamashita, Hasan Rajabi, Atsushi Fushimi, Mark D. Long, Wei Li, Atrayee Bhattacharya, Rehan Ahmad, Mototsugu Oya, Song Liu, Donald Kufe
Summary: MUC1-C associates with E2F1 and activates a novel pathway related to prostate cancer stem cell function.
Article
Cell Biology
Saul Carcamo, Christie B. Nguyen, Elena Grossi, Dan Filipescu, Aktan Alpsoy, Alisha Dhiman, Dan Sun, Sonali Narang, Jochen Imig, Tiphaine C. Martin, Ramon Parsons, Iannis Aifantis, Aristotelis Tsirigos, Julio A. Aguirre-Ghiso, Emily C. Dykhuizen, Dan Hasson, Emily Bernstein
Summary: ARID2 is the most commonly mutated member of the SWI/SNF complex in melanoma. Its deficiency leads to defective assembly of the PBAF complex and redistribution of the BAF complex. ARID2 depletion results in reduced chromatin accessibility and gene expression in certain regions, while enhancers occupied by the BAF complex gain accessibility and gene expression related to invasion. The occupancy of melanoma-relevant transcription factors is affected by altered accessibility, and correlates significantly with the observed transcriptional changes. Furthermore, ARID2-deficient cells acquire the ability to colonize distal organs in multiple animal models.
Review
Genetics & Heredity
Bercin K. Cenik, Ali Shilatifard
Summary: Trithorax group proteins, including COMPASS histone H3 lysine 4 methyltransferase complexes and SWI/SNF chromatin remodelling complexes, play crucial roles in gene regulation, development, and disease. Misregulation of these complexes through genetic abnormalities can lead to pathologies such as developmental disorders and malignancies.
NATURE REVIEWS GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Rakesh Kumar Sahu, Sakshi Singh, Raghuvir Singh Tomar
Summary: The SWI/SNF and RSC complexes play a critical role in gene expression by displacing nucleosomes, particularly in inducing stress-responsive transcription programs such as heat shock response genes and unfolded protein response. Their cooperation at promoters of UPR, HSP, and PQC genes under proteotoxic conditions suggests a functional synergy in inducing stress-responsive genes.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2021)
Article
Obstetrics & Gynecology
Fiona K. Smith, Ijeoma Agu, Shivani Murarka, Gazala Siddiqui, Francisco J. Orejuela, Tristi W. Muir, Danielle D. Antosh
Summary: This study found that there are differences in barriers to care for patients presenting to urogynecologists in private and public healthcare settings. Patients in private settings were mainly hindered by not knowing how to see a specialist, while patients in public settings were hindered by inability to get a closer appointment time. Additionally, patients in public settings were more likely to cite lack of health care coverage as a barrier to care.
FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
(2021)
Correction
Biochemistry & Molecular Biology
Matthew J. McBride, Nazar Mashtalir, Evan B. Winter, Hai T. Dao, Martin Filipovski, Andrew R. D'Avino, Hyuk-Soo Seo, Neil T. Umbreit, Roodolph St Pierre, Alfredo M. Valencia, Kristin Qian, Hayley J. Zullow, Jacob D. Jaffe, Sirano Dhe-Paganon, Tom W. Muir, Cigall Kadoch
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
John D. Bagert, Michelle M. Mitchener, Agata L. Patriotis, Barbara E. Dul, Felix Wojcik, Benjamin A. Nacev, Lijuan Feng, C. David Allis, Tom W. Muir
Summary: The research has identified numerous histone mutations in cancer, particularly in the context of chromatin remodeling and gene regulation pathways. These mutations may play a critical role in disease development by perturbing nucleosome remodeling processes.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hai T. Dao, Hengyuan Liu, Nazar Mashtalir, Cigall Kadoch, Tom W. Muir
Summary: This study reports a strategy for controlling the orientation of asymmetric nucleosomes and hexasomes, providing an efficient method for studying gene regulation. By using truncated DNA templates and DNA ligation, the researchers successfully prepared desymmetrized mononucleosomes and oligonucleosomes with varied DNA sequences and histone compositions. Using this technology, they investigated the impact of asymmetry on chromatin remodeling and found that cancer-associated histone mutations can cause aberrant chromatin structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Bradley J. Lukasak, Robert E. Thompson, Michelle M. Mitchener, Vanessa J. Feng, John D. Bagert, Tom W. Muir
Summary: In this study, the SpyCatcher/SpyTag system was used to assemble desymmetrized nucleoprotein complexes. This method allows for the generation of nucleosomes with asymmetric modifications and facilitates the investigation of the effects of nucleosome asymmetry on chromatin remodeling processes and histone enzyme activity.
ACS CENTRAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Hai T. Dao, Linh T. D. Pham
Summary: Structural and biochemical studies have shown that the nucleosome acidic patch plays a crucial role in regulating the function of nuclear proteins. Different remodeler families interact with the acidic patch in distinct ways, leading to specific remodeling outcomes. The impact of cancer-related histone mutations on nucleosome remodeling is not well understood. Recent advancements in chromatin reconstitution have shed light on the effects of acidic patch mutations on chromatin structure.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Multidisciplinary Sciences
Aishan Zhao, Steven P. Bodine, Qian Xie, Boyuan Wang, Geeta Ram, Richard P. Novick, Tom W. Muir
Summary: This study reveals the involvement of membrane protease regulator of agr QS (MroQ) in the production of autoinducing peptide (AIP) in Staphylococcus aureus. It also uncovers the different roles of MroQ in different agr specificity groups, enhancing our understanding of the agr response and Staphylococcus aureus virulence.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Martin Filipovski, Jelly H. M. Soffers, Seychelle M. Vos, Lucas Farnung
Summary: This study reports the structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex and reveals the direct role of Pol II and transcription elongation factors in nucleosome retention, explaining how nucleosomes are retained to maintain the chromatin structure of actively transcribed genes.
Article
Chemistry, Multidisciplinary
Giridhar Sekar, Adam J. Stevens, Anahita Z. Mostafavi, Pulikallu Sashi, Tom W. Muir, David Cowburn
Summary: Split intein-mediated protein trans-splicing (PTS) is a widely used method in chemical biology and biotechnology for traceless and specific protein ligation. The efficiency of PTS can be limited by external residues flanking the intein. In this study, a recently developed atypically split intein (Cat) was further modified to enhance its PTS activity in the presence of unfavorable N-extein residues. The mechanism behind the enhanced activity was explored using nuclear magnetic resonance spectroscopy and molecular dynamics simulations, highlighting the contribution of a conserved histidine residue. This enhanced extein tolerance of Cat* expands the applicability of atypically split inteins and reveals common principles of extein dependence.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Michelle M. Mitchener, Tom W. Muir
Summary: Research over the past decade has revealed a new layer of epigenetic dysregulation, uncovering the association between somatic missense mutations in histones and human pathologies, especially cancer. While some of these mutations are believed to be key drivers of cancer, the effects of the majority of them on disease onset and progression are still unclear. Studies have shown that even at low dosage, histone mutants can corrupt chromatin states, providing insights into the intricate mechanisms of epigenetic control.
