Article
Oncology
Tianchu Wang, Ryan T. Wagner, Ryan A. Hlady, Xiaoyu Pan, Xia Zhao, Sungho Kim, Liguo Wang, Jeong-Heon Lee, Huijun Luo, Erik P. Castle, Douglas F. Lake, Thai H. Ho, Keith D. Robertson
Summary: SETD2 mutation and/or loss of H3K36me3 is associated with metastasis and poor outcome in clear cell renal cell carcinoma (ccRCC) patients. Inactivation of SETD2 drives epithelial-to-mesenchymal transition (EMT), promoting migration, invasion, and stemness independently of transforming growth factor-beta. Upregulated transcription factors, including SOX2, POU2F2, and PRRX1, upon SETD2 loss contribute to the EMT and stemness phenotypes. These findings provide insights into the cellular and molecular mechanisms linking SETD2 loss to ccRCC metastasis.
MOLECULAR ONCOLOGY
(2023)
Article
Plant Sciences
Hasan Mehraj, Satoshi Takahashi, Naomi Miyaji, Ayasha Akter, Yutaka Suzuki, Motoaki Seki, Elizabeth S. Dennis, Ryo Fujimoto
Summary: Covalent modifications of histone proteins, such as H3K4me3 and H3K36me3, are found to regulate gene expression in Brassica rapa L. Two lines of this species showed enrichment of these histone marks at transcription start sites, with gene expression levels being influenced by them. Genes with both H3K4me3 and H3K36me3 typically showed constitutive high expression levels. Additionally, bivalent active and repressive histone modifications were observed in some genes.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Veronica Uribe-Etxebarria, Jose Ramon Pineda, Patricia Garcia-Gallastegi, Alice Agliano, Fernando Unda, Gaskon Ibarretxe
Summary: The dental pulp of permanent human teeth contains stem cells known as Dental Pulp Stem Cells (DPSCs), which have the ability to differentiate into multiple cell lineages. The pluripotency core factors expressed by these cells, as well as the involvement of signaling pathways like Notch and Wnt, contribute to their stemness maintenance. Utilizing recombinant proteins, pharmacological modulators, serum-free media, and appropriate scaffolds, researchers can optimize the potency of DPSCs without genetic modification. This review highlights the mechanisms and regulatory pathways responsible for maintaining stemness in DPSCs, drawing interesting parallels with pluripotent stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yuan Fang, Yin Tang, Yanjun Zhang, Yixin Pan, Junqi Jia, Zhongxing Sun, Weiwu Zeng, Jiaqi Chen, Ying Yuan, Dong Fang
Summary: Epigenetics, especially histone marks, plays a crucial role in regulating gene expression beyond DNA sequences. NSD1 depletion leads to both up- and down-regulation of gene expression, with an increase in H3K27ac correlating with the decrease of H3K36me2. NSD1 acts as a 'safeguard' by depositing H3K36me2 and recruiting HDAC1 at active enhancers to prevent further activation of active enhancer-associated genes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mariola Ferreras-Gutierrez, Belen Chaves-Arquero, Amaia Gonzalez-Magana, Nekane Merino, Ignacio Amusategui-Mateu, Sonia Huecas, Francisco J. Medrano, Francisco J. Blanco
Summary: Proteins of the ING family regulate chromatin transcription by recruiting remodeling complexes to sites with H3K4me3 modification. ING3, an oncoprotein, facilitates histone acetylation and forms homodimers with an antiparallel coiled-coil fold. The crystal structure of ING3's PHD domain reveals its interaction with H3K4me3 and the impact of mutations on histone recognition.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Isabelle A. Engelberg, Jiuyang Liu, Jacqueline L. Norris-Drouin, Stephanie H. Cholensky, Samantha A. Ottavi, Stephen Frye, Tatiana G. Kutateladze, Lindsey James
Summary: PHF1, an accessory component of polycomb repressive complex 2, recognizes the active chromatin mark H3K36me3 for transcriptional regulation. UNC6641 is a peptidomimetic antagonist of PHF1 Tudor domain, capable of binding both PHF1 and PHF19 with high potency, providing insights into the binding mechanism through crystal structure and other data. Additionally, UNC6641 facilitates the development of a high-throughput assay for identifying small molecule binders of PHF1.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Liquan Jin, Ziting Su, Shan Huang, Yunbo Tan, Isack George Mrema, Yiming Chen
Summary: This study aimed to investigate the function and expression of H3K36me3 and SETD2 during the differentiation of HOCs into cholangiocytes. HOCs were isolated from mice and cultured with specific factors. The protein levels of SETD2 and H3K36me3 were quantified, and the results showed that the expression of CK-19 increased, while OV-6 decreased, with a concurrent increase in SETD2 and H3K36me3 levels, indicating their potential involvement in differentiation.
MOLECULAR MEDICINE REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Saikat Bhattacharya, Jeffrey J. Lange, Michaella Levy, Laurence Florens, Michael P. Washburn, Jerry L. Workman
Summary: SETD2 has multiple long disordered regions that cumulatively destabilize the protein by promoting proteasomal degradation, playing a crucial role in regulating its stability and half-life. The disordered regions can also exacerbate phase-separation behavior in SETD2, particularly upon removal of the N-terminal segment.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Franziska Greulich, Michael Wierer, Aikaterini Mechtidou, Omar Gonzalez-Garcia, N. Henriette Uhlenhaut
Summary: The SETD1A/COMPASS histone methyltransferase complex is highly enriched in activated mouse macrophages and cooperates with the glucocorticoid receptor (GR) to mediate anti-inflammatory effects. Their interaction leads to transcriptional changes in subsets of macrophage target genes.
Article
Biochemistry & Molecular Biology
Liangbing Yuan, Xin Song, Lu Zhang, Yaoguang Yu, Zhenwei Liang, Yawen Lei, Jiuxiao Ruan, Bin Tan, Jun Liu, Chenlong Li
Summary: The study reveals that the transcriptional repressors VAL1 and VAL2 recruit PRC2 to target loci in Arabidopsis thaliana. They physically interact with PRC2 catalytic subunits SWN and CLF, colocalize at target loci, and regulate H3K27me3 levels, affecting transcription.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Genetics & Heredity
Callum J. J. Fraser, Simon K. K. Whitehall
Summary: This article mainly discusses the role of heterochromatin in fungal plant pathogens, particularly in host colonization and genome plasticity. The article analyzes the association between effector genes and heterochromatic regions enriched with transposable elements and explores the research progress in this field.
FRONTIERS IN GENETICS
(2022)
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)
Article
Immunology
Qi An, Chenyan Sun, Ruidi Li, Shuhui Chen, Xinpei Gu, Shuhong An, Zhaojin Wang
Summary: The study reveals that CGRP is involved in the pathogenesis of neuropathic pain by regulating microglial activation through EZH2-mediated H3K27me3 in the spinal dorsal horn. The findings demonstrate that CGRP treatment and chronic constriction injury lead to increased expressions of key mediators of microglial activation in the spinal dorsal horn and cultured microglial cells.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
John R. Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T. Bedford, Xiaodong Cheng
Summary: The N-terminal half of PHF2 contains a PHD and a Jumonji domain, which can recognize H3 trimethylated at lysine 4 and VRK1. The Jumonji domain can erase dimethylation mark from H3K9me2 at select promoters. The N-terminal half of PHF2 binds to H3 and VRK1 peptides containing K4me3 with higher affinities than the isolated PHD domain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
Qianyun Mei, Qi Yu, Xin Li, Jianguo Chen, Xilan Yu
Summary: Histone loss during yeast aging compromises telomere silencing by promoting Sir2 degradation through autophagy. Reduction of core histones enhances autophagy pathway, further accelerating autophagy-mediated Sir2 degradation. Screening of histone mutants and one histone modification identifies regulators of telomere silencing via modulation of core histones-autophagy-Sir2 axis.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biotechnology & Applied Microbiology
Aaron R. Lim, Benjamin G. Vincent, Alissa M. Weaver, W. Kimryn Rathmell
Summary: This study found that tyrosine kinase inhibitors Sunitinib and Axitinib can increase the secretion of extracellular vesicles (EVs) from human renal cell carcinoma cells. These EVs contained enriched metabolic proteins, particularly GLUT1, which led to higher glucose uptake and glycolytic metabolism. Overall, the findings suggest that these tyrosine kinase inhibitors alter metabolic cargo and activity in RCC EVs.
CANCER GENE THERAPY
(2022)
Review
Immunology
Bradley I. Reinfeld, W. Kimryn Rathmell, Tae Kon Kim, Jeffrey C. Rathmell
Summary: The new hallmarks of cancer relating to metabolism have shown that tumor cells not only benefit from altered cellular energetics, but also create an immunosuppressive microenvironment that promotes their own growth and progression. Development of therapies targeting cancer metabolism needs to carefully consider the balance between inhibiting tumor growth and preserving antitumor immunity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Microbiology
Connor J. Beebout, Gabriella L. Robertson, Bradley Reinfeld, Alexandra M. Blee, Grace H. Morales, John R. Brannon, Walter J. Chazin, W. Kimryn Rathmell, Jeffrey C. Rathmell, Vivian Gama, Maria Hadjifrangiskou
Summary: Uropathogenic Escherichia coli rewires host cell metabolism, promotes aerobic glycolysis, and protects intracellular bacteria during urinary tract infection.
NATURE MICROBIOLOGY
(2022)
Article
Surgery
Naira Baregamian, Konjeti R. Sekhar, Evan S. Krystofiak, Maria Vinogradova, Giju Thomas, Emmanuel Mannoh, Carmen C. Solorzano, Colleen M. Kiernan, Anita Mahadevan-Jansen, Naji Abumrad, Michael L. Freeman, Vivian L. Weiss, Jeffrey C. Rathmell, W. Kimryn Rathmell
Summary: By using fine needle aspiration, the researchers have successfully established 3-dimensional endocrine organoid models that accurately simulate the complex tumor microenvironment of thyroid, parathyroid, and adrenal neoplasms, while maintaining cytokine production and near-infrared autofluorescence properties.
Correction
Multidisciplinary Sciences
Wei Jiao, Gurnit Atwal, Paz Polak, Rosa Karlic, Edwin Cuppen, Alexandra Danyi, Jeroen de Ridder, Carla van Herpen, Martijn P. Lolkema, Neeltje Steeghs, Gad Getz, Quaid D. Morris, Lincoln D. Stein
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Yulia Rubanova, Ruian Shi, Caitlin F. Harrigan, Roujia Li, Jeff Wintersinger, Nil Sahin, Amit G. Deshwar, Quaid D. Morris
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Kelsey Voss, Allison E. Sewell, Evan S. Krystofiak, Katherine N. Gibson-Corley, Arissa C. Young, Jacob H. Basham, Ayaka Sugiura, Emily N. Arner, William N. Beavers, Dillon E. Kunkle, Megan E. Dickson, Gabriel A. Needle, Eric P. Skaar, W. Kimryn Rathmell, Michelle J. Ormseth, Amy S. Major, Jeffrey C. Rathmell
Summary: T cells in systemic lupus erythematosus (SLE) exhibit metabolic abnormalities, with excess iron playing a potential role in SLE pathogenesis. The transferrin receptor (CD71) is critical for T(H)1 cells and inhibitory for induced regulatory T cells (iT(regs)). Increased CD71 expression and iron uptake were observed in activated T cells, particularly in SLE-prone T cells. Blocking CD71 reduced intracellular iron, mTORC1 signaling, and the production of T(H)1 and T(H)17 cells, while enhancing iT(regs) and IL-10 secretion. In vivo treatment targeting CD71 reduced kidney pathology in SLE-prone mice. CD71 expression on T(H)17 cells correlated with disease severity in SLE patients. Thus, T cell iron uptake via CD71 contributes to T cell dysfunction and can be targeted to limit SLE-associated pathology.
SCIENCE IMMUNOLOGY
(2023)
Review
Oncology
Catherine C. Fahey, Thomas J. Gracie, Douglas B. Johnson
Summary: The advent of immunotherapy has revolutionized cancer treatment, showing anti-tumor efficacy in various cancer types. However, immune-related adverse events (irAEs) pose risks, and there is currently no approved biomarkers for patient categorization. This review provides a comprehensive summary of ICI treatment and irAEs, including the use of ICI, risk identification, irAE development, biomarker research, prevention opportunities, management strategies, and future directions. It is unlikely to have a universal approach for categorizing irAE risk, but improving management and prophylaxis are achievable goals.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Editorial Material
Cell Biology
Kanishk Jain, Brian D. Strahl
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Letter
Cell Biology
Zhenzhen Chen, Taylor Lundy, Zhongliang Zhu, Victoria E. Hoskins, Jiahai Zhang, Xuebiao Yao, Brian D. Strahl, Chao Xu
Article
Immunology
Lihong Wang-Bishop, Blaise R. Kimmel, Verra M. Ngwa, Matthew Z. Madden, Jessalyn J. Baljon, David C. Florian, Ann Hanna, Lucinda E. Pastora, Taylor L. Sheehy, Alexander J. Kwiatkowski, Mohamed Wehbe, Xiaona Wen, Kyle W. Becker, Kyle M. Garland, Jacob A. Schulman, Daniel Shae, Deanna Edwards, Melissa M. Wolf, Rossane Delapp, Plamen P. Christov, Kathryn E. Beckermann, Justin M. Balko, W. Kimryn Rathmel, Jeffrey C. Rathmell, Jin Chen, John T. Wilson
Summary: The tumor-associated vasculature presents obstacles for T cell infiltration and effective tumor control. The activation of the STING pathway is associated with T cell infiltration in human cancers. Therefore, STING-activating nanoparticles (STANs) were evaluated for their effect on the tumor vasculature and T cell infiltration. In mouse tumor models, intravenous administration of STANs promoted vascular normalization, resulting in improved T cell infiltration and antitumor function.
SCIENCE IMMUNOLOGY
(2023)
Correction
Oncology
Robert Hapke, Lindsay Venton, Kristie Lindsay Rose, Quanhu Sheng, Anupama Reddy, Rebecca Prather, Angela Jones, W. Kimryn Rathmell, Scott M. Haak
Article
Medicine, General & Internal
Rachel W. Walmer, Victor S. Ritter, Anush Sridharan, Sandeep K. Kasoji, Ersan Altun, Ellie Lee, Kristen Olinger, Sean Wagner, Roshni Radhakrishna, Kennita A. Johnson, W. Kimryn Rathmell, Bahjat Qaqish, Paul A. Dayton, Emily H. Chang
Summary: The accuracy of CEUS in characterizing cystic and solid kidney lesions in CKD patients was investigated in this study. It was found that CEUS is a potential low-risk option for screening kidney lesions, particularly in CKD IV/V patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Correction
Cell Biology
Zhenzhen Chen, Taylor Lundy, Zhongliang Zhu, Victoria E. E. Hoskins, Jiahai Zhang, Xuebiao Yao, Brian D. D. Strahl, Chao Xu
Article
Biochemistry & Molecular Biology
Catherine C. Fahey, Caroline A. Nebhan, Sally York, Nancy B. Davis, Paula J. Hurley, Jennifer B. Gordetsky, Kerry R. Schaffer
Summary: Penile squamous cell carcinoma is a rare disease with limited treatment options, especially in the metastatic setting. This case report highlights the potential of using the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV) as a treatment option for metastatic penile squamous cell carcinoma. Further studies are needed to establish high-quality evidence for guiding treatment decisions in this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)