Article
Oncology
Andrew VonHandorf, Hesbon A. Zablon, Alvaro Puga
Summary: Cells adjust gene expression by modulating chromatin architecture in response to environmental stimuli, while chromium promotes disruption of gene expression by targeting chromatin structure.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yao Wang, Sabine Groeger, Jiawen Yong, Sabine Ruf
Summary: Orthodontic tooth movement is a complex process involving inflammation and immune responses. Macrophages, as mechanically sensitive immune cells, may be activated by orthodontic force and play a role in orthodontic root resorption. The activation of macrophages is associated with H3 histone acetylation and M2 polarization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xu Pan, Xin Li, Jie Sun, Zhiying Xiong, Haoyu Hu, Shangwei Ning, Hui Zhi
Summary: This study reveals that DNA methylation can drive tissue-specific enhancer basal transcription and target gene expression in human cancers. By integrating methylome, transcriptome, and 3D genomic data, enhancer methylation triplets were identified and regulatory patterns within them were dissected. Cancer-specific core TFs regulated by enhancers were observed to shape enhancer methylation forming enhancer methylation-driven CRCs (emCRCs).
Article
Medicine, Research & Experimental
Minhong Huang, Dan Lou, Adhithiya Charli, Dehui Kong, Huajun Jin, Gary Zenitsky, Vellareddy Anantharam, Arthi Kanthasamy, Zhibin Wang, Anumantha G. Kanthasamy
Summary: Research shows that mitochondrial dysfunction leads to increased H3K27ac acetylation in dopaminergic neuronal models of PD, opening vulnerable epigenomic loci, which is validated in PD-related neurodegenerative models and postmortem PD brains.
Article
Immunology
Dorota Iwaszkiewicz-Grzes, Magdalena Piotrowska, Mateusz Gliwinski, Zuzanna Urban-Wojciuk, Piotr Trzonkowski
Summary: The study revealed that insulin beta chain peptide 9-23 favored specific Tregs expression, while whole insulin activated both Tregs and Teffs. Tregs SPECB:9-23 showed the highest level of expression in crucial genes and lower methylation levels.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alessa R. Ringel, Quentin Szabo, Andrea M. Chiariello, Konrad Chudzik, Robert Schopflin, Patricia Rothe, Alexandra L. Mattei, Tobias Zehnder, Dermot Harnett, Verena Laupert, Simona Bianco, Sara Hetzel, Juliane Glaser, Mai H. Q. Phan, Magdalena Schindler, Daniel M. Ibrahim, Christina Paliou, Andrea Esposito, Cesar A. Prada-Medina, Stefan A. Haas, Peter Giere, Martin Vingron, Lars Wittler, Alexander Meissner, Mario Nicodemi, Giacomo Cavalli, Frederic Bantignies, Stefan Mundlos, Michael I. Robson
Summary: Regulatory landscapes play a crucial role in complex developmental gene expression. This study investigated how a specific gene, Zfp42, emerged in an ancient vertebrate topologically associated domain (TAD) without disrupting the expression of its neighboring gene, Fat1. The findings suggest that the independent expression of Zfp42 is driven by chromatin activity and context-dependent DNA methylation.
Article
Biochemistry & Molecular Biology
Alex J. McCann, Jieqiong Lou, Mehdi Moustaqil, Matthew S. Graus, Ailisa Blum, Frank Fontaine, Hui Liu, Winnie Luu, Paulina Rudolffi-Soto, Peter Koopman, Emma Sierecki, Yann Gambin, Frederic A. Meunier, Zhe Liu, Elizabeth Hinde, Mathias Francois
Summary: The study reveals that the mutant SOX18(RaOp) disrupts the system through molecular interferences, impairing the functions of wild-type SOX18 protein, and amplifying the dominant-negative effect by poisoning the interactome of its wild-type counterpart.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Zoe S. Walters, Ewa Aladowicz, Barbara Villarejo-Balcells, Gary Nugent, Joanna L. Selfe, Paul Eve, Julian Blagg, Olivia Rossanese, Janet Shipley
Summary: Rhabdomyosarcomas (RMS) are soft tissue sarcomas predominantly found in children, and current treatments have severe side effects and poor outcomes, necessitating the discovery of novel, more targeted therapies. High expression of histone demethylases, particularly KDM4B, supports proliferation of RMS cells, and sustained knockdown of KDM4B can lead to functional compensation by KDM4A. Targeting both KDM4A and KDM4B is shown to be effective in killing RMS cells and overcoming functional redundancy in order to elicit strong therapeutic responses.
News Item
Biochemistry & Molecular Biology
Kanishk Jain, Brian D. Strahl
Summary: High-throughput biochemical and biological analyses of disease-associated histone mutations reveal key residues in globular cores that affect chromatin remodeling, nucleosome stability, and stem cell pluripotency.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alexandre P. Marand, Zongliang Chen, Andrea Gallavotti, Robert J. Schmitz
Summary: By analyzing single-cell genomics data from six maize organs, researchers identified cis-regulatory factors and trans-regulatory factors, revealing the crucial role of cell-type-specific regulatory elements in gene expression regulation, and developed the single-cell analysis software Socrates for studying cis-regulatory variation in various species.
Article
Biodiversity Conservation
Dorothee Hodapp, Irene T. Roca, Dario Fiorentino, Cristina Garilao, Kristin Kaschner, Kathleen Kesner-Reyes, Birgit Schneider, Joachim Segschneider, Adam T. Kocsis, Wolfgang Kiessling, Thomas Brey, Rainer Froese
Summary: Driven by climate change, marine biodiversity is undergoing rapid changes, faster than those in terrestrial ecosystems. Understanding the impact of these changes on future marine life is crucial for conservation, due to increasing demands for marine resources. Our analysis predicts a decline in core habitat area for many species, with a net loss of 50% for almost half of all marine species by 2100 under the high-emission scenario. Distributional reorganization will lead to gaps around the equator for a significant number of marine species, disrupting their continuous ranges. Invasion rates in higher latitudes and polar regions will also introduce new predators and change ecosystem and food web structure. The degree of reorganization and its consequences will depend on greenhouse gas emission pathway.
GLOBAL CHANGE BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Alexandre M. J. Gomila, Gonzalo Perez-Mejias, Alba Nin-Hill, Alejandra Guerra-Castellano, Laura Casas-Ferrer, Sthefany Ortiz-Tescari, Antonio Diaz-Quintana, Josep Samitier, Carme Rovira, Miguel A. De la Rosa, Irene Diaz-Moreno, Pau Gorostiza, Marina Giannotti, Anna Lagunas
Summary: The authors investigate the mechanism of electron transfer and show how phosphorylation regulates the interactions between mitochondrial cytochrome c and cytochrome bc(1). They demonstrate that phosphorylation impairs long-range electron transfer, shortens the distance between the protein partners, strengthens their interaction, and disrupts equilibrium.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Chenchen Feng, Chao Song, Yong Jiang, Jun Zhao, Jian Zhang, Yuezhu Wang, Mingxue Yin, Jiang Zhu, Bo Ai, Qiuyu Wang, Fengcui Qian, Yuexin Zhang, Desi Shang, Jiaqi Liu, Chunquan Li
Summary: This study identifies core transcription factors and their regulatory circuits in large cell/tissue samples. The local module analysis highlights the essential functions and prognostic performance of the core circuitry. Tissue-specific core circuits are related to cell identity and exhibit potential for disease markers and cancer immunotherapy.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Cell Biology
Lu-Qiang Zhang, Guo-Liang Fan, Jun-Jie Liu, Li Liu, Qian-Zhong Li, Hao Lin
Summary: This study analyzed the distribution patterns of 11 HM signals in CML cell lines compared to normal cell lines, and found that H3K79me2 and H3K36me3 may be core HMs influencing the expression changes of CML-related genes. The research suggests that these two HMs could be crucial for the clinical treatment of CML.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Sophie Rousseaux, Nicolas Reynoird, Saadi Khochbin
Summary: The functional characterization of the BRD4-NUT fusion protein in NUT Carcinoma cells reveals its role in histone hyperacetylation and chromatin binding through interaction with p300, leading to histone replacement and compact packaging of the male genome.
Article
Immunology
Xuyong Chen, Benjamin Sunkel, Meng Wang, Siwen Kang, Tingting Wang, J. N. Rashida Gnanaprakasam, Lingling Liu, Teresa A. Cassel, David A. Scott, Ana M. Munoz-Cabello, Jose Lopez-Barneo, Jun Yang, Andrew N. Lane, Gang Xin, Benjamin Z. Stanton, Teresa W. -M. Fan, Ruoning Wang
Summary: Effective T cell-mediated immune responses require proper allocation of metabolic resources and epigenetic control. Our study revealed that tricarboxylic acid cycle flux fuels biosynthetic processes and controls the ratio of succinate/alpha-ketoglutarate to modulate T cell inflammation. SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, but replenishing the nucleoside pool partially relieved the dependence of T cells on SDH/complex II. SDH deficiency induced a proinflammatory gene signature and promoted T helper 1 and T helper 17 lineage differentiation by increasing succinate/alpha-KG ratio. SDH/complex II plays a role in allocating carbon resources and epigenetic regulation in T cell proliferation and inflammation.
SCIENCE IMMUNOLOGY
(2022)
Review
Cell Biology
Meng Wang, Benjamin D. Sunkel, William C. Ray, Benjamin Z. Stanton
Summary: In the past decade, sequence-based methods have been used to understand chromosome organization. Advances in single molecule imaging have revealed cell-to-cell chromatin structural variation, which raises the question of whether altered chromatin structure can drive tumorigenesis. Recent studies have shown that deregulation of genome structure is characteristic in distinct classes of chromatin-driven tumors.
BMC MOLECULAR AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Silvia Pomella, Matteo Cassandri, Ombretta Melaiu, Francesco Marampon, Marco Gargari, Vincenzo Campanella, Rossella Rota, Giovanni Barillari
Summary: We analyzed the genomic and transcriptomic status of DNA damage response (DDR) genes in oral squamous cell carcinoma (OSCC) and identified a signature of eight DDR genes that could predict OSCC response to antitumor compounds. Our results also showed correlations between the expression of certain DDR genes and OSCC grading and human papilloma virus infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Clara Perrone, Silvia Pomella, Matteo Cassandri, Michele Pezzella, Stefano Giuliani, Tecla Gasperi, Antonella Porrazzo, Anna Alisi, Anna Pastore, Silvia Codenotti, Alessandro Fanzani, Giovanni Barillari, Libenzio Adrian Conti, Biagio De Angelis, Concetta Quintarelli, Paolo Mariottini, Franco Locatelli, Francesco Marampon, Rossella Rota, Manuela Cervelli
Summary: Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma with two molecular subtypes, fusion-positive (FP) and fusion-negative (FN). While FP-RMS has a poor prognosis, FN-RMS shows resistance to chemotherapy and radiation therapy due to cytogenetic abnormalities and RAS pathway mutations. This study found that low expression of spermine oxidase (SMOX) is associated with worse outcomes in FN-RMS patients and is downregulated in FN-RMS cell lines. Forced expression of SMOX in high-risk FN-RMS cell lines inhibited tumor growth, induced cell cycle arrest and apoptosis, and increased DNA damage response. These findings suggest that SMOX induction could be a potential strategy to sensitize FN-RMS to ionizing radiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Hematology
Katherine E. Masih, Rebecca A. Gardner, Hsien-Chao Chou, Abdalla Abdelmaksoud, Young K. Song, Luca Mariani, Vineela Gangalapudi, Berkley E. Gryder, Ashley L. Wilson, Serifat O. Adebola, Benjamin Z. Stanton, Chaoyu Wang, David Milewski, Yong Yean Kim, Meijie Tian, Adam Tai -Chi Cheuk, Xinyu Wen, Yue Zhang, Gregoire Altan-Bonnet, Michael C. Kelly, Jun S. Wei, Martha L. Bulyk, Michael C. Jensen, Rimas J. Orentas, Javed Khan
Editorial Material
Biochemistry & Molecular Biology
Alexi Tallan, Rachel A. Hoffman, Benjamin Z. Stanton
Review
Biochemistry & Molecular Biology
Ombretta Melaiu, Gianluca Vanni, Ilaria Portarena, Chiara Adriana Pistolese, Lucia Anemona, Silvia Pomella, Roberto Bei, Oreste Claudio Buonomo, Mario Roselli, Alessandro Mauriello, Giovanni Barillari
Summary: Immune checkpoint inhibitors have limited clinical activity as monotherapy against breast cancer, and novel combinatorial strategies are being investigated to improve treatment response. The abnormal vasculature in breast cancer is associated with immune suppression and hampers drug delivery and immune cell trafficking. Combining immune checkpoint inhibitors with tumor vessel normalizing agents shows promise in enhancing antitumor immune responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Silvia Pomella, Sara G. Danielli, Rita Alaggio, Willemijn B. Breunis, Ebrahem Hamed, Joanna Selfe, Marco Wachtel, Zoe S. Walters, Beat W. Schaefer, Rossella Rota, Janet M. Shipley, Simone Hettmer
Summary: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, characterized by aberrant muscle differentiation. Abnormalities in the regulatory transcription factors (MRFs) involved in skeletal muscle development contribute to tumorigenesis in RMS. Core regulatory circuitries (CRCs) and hierarchically organized subsets of cells play a role in maintaining the disease-driving fusion oncogene and promoting malignancy in RMS. Understanding the genetic and epigenetic framework of abnormal muscle differentiation in RMS provides insights into its mechanisms and potential therapeutic strategies.
Article
Biochemical Research Methods
Emma J. Chory, Meng Wang, Michele Ceribelli, Aleksandra M. Michalowska, Stefan Golas, Erin Beck, Carleen Klumpp-Thomas, Lu Chen, Crystal McKnight, Zina Itkin, Kelli M. Wilson, David Holland, Sanjay Divakaran, James Bradner, Javed Khan, Berkley E. Gryder, Craig J. Thomas, Benjamin Z. Stanton
Summary: We conducted a comprehensive study on drug synergy in acute myeloid leukemia (AML), using a panel of cell lines representing different subtypes. Our study provides a valuable resource for the community, offering many unexpected synergistic drug combinations and open source code for automation and analysis. We identified drug synergies that affect the chromatin state, particularly in relation to the modification of histone H3 lysine-27. Additionally, we developed an open source high throughput methodology that allows multidimensional drug screening with widely accessible equipment.
Article
Biochemistry & Molecular Biology
Meng Wang, Prethish Sreenivas, Benjamin D. Sunkel, Long Wang, Myron Ignatius, Benjamin Z. Stanton
Summary: Researchers analyzed the chromatin structure of pediatric soft tissue cancer and found that it plays a crucial role in tumor proliferation, providing insights for potential therapy options.
Article
Biochemistry & Molecular Biology
Prethish Sreenivas, Long Wang, Meng Wang, Anil Challa, Paulomi Modi, Nicole Rae Hensch, Berkley Gryder, Hsien-Chao Chou, Xiang R. Zhao, Benjamin Sunkel, Rodrigo Moreno-Campos, Javed Khan, Benjamin Z. Stanton, Myron S. Ignatius
Summary: RMS is a pediatric malignancy of muscle cells, and NOTCH1 is an oncogene that promotes self-renewal and blocks differentiation in RMS. The study suggests that SNAI2 and CTCF maintain a sub-topologically associating domain boundary, which promotes NOTCH1 expression. Suppression of SNAI2 results in cell loss, but a few surviving clones can re-establish NOTCH1 expression.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Meeting Abstract
Oncology
Katherine E. Masih, Rebecca Gardner, Hsien-Chao Chou, Abdalla Abdelmaksoud, Young K. Song, Luca Mariani, Vineela Gangalapudi, Berkley E. Gryder, Ashley Wilson, Serifat O. Adebola, Benjamin Z. Stanton, Chaoyu Wang, Xinyu Wen, Gregoire Altan-Bonnet, Michael C. Kelly, Jun S. Wei, Martha L. Bulyk, Michael C. Jensen, Rimas J. Orentas, Javed Khan