Article
Developmental Biology
Haley E. Brown, Brandon P. Weasner, Bonnie M. Weasner, Justin P. Kumar
Summary: This study reveals that reduced Polycomb expression leads to abnormal development in Drosophila imaginal discs, causing the transformation of eyes into wings. Disruption of the Vestigial-Scalloped complex not only blocks wing formation, but also results in the organization of multiple domains into other imaginal discs and tissues.
Review
Entomology
Jean-Michel Gibert, Frederique Peronnet
Summary: Drosophila melanogaster has played a crucial role in epigenetics, studying changes in gene function inherited through mitosis or meiosis that are not due to changes in the DNA sequence. By analyzing simple phenotypes, such as bristle position or cuticle pigmentation, identification of mutated genes led to the discovery of major chromatin regulators that are often conserved in distantly related organisms.
Article
Cell Biology
Ludivine Raby, Pamela Volkel, Shaghayegh Hasanpour, Julien Cicero, Robert-Alain Toillon, Eric Adriaenssens, Isabelle Van Seuningen, Xuefen Le Bourhis, Pierre-Olivier Angrand
Summary: This study reports on a zebrafish line with a null allele of eed, a key component of PRC2, and reveals severe defects in digestive organs and brain neuronal differentiation in homozygous eed-deficient mutants, leading to death. Additionally, loss of PRC2 function in zebrafish increases larval activity and highlights its potential as a model for studying human pathologies linked to PRC2 dysfunction and reduced H3K27me3 levels.
Article
Cell Biology
Marc Garcia-Montolio, Cecilia Ballare, Enrique Blanco, Arantxa Gutierrez, Sergi Aranda, Antonio Gomez, Chung H. Kok, David T. Yeung, Timothy P. Hughes, Pedro Vizan, Luciano Di Croce
Summary: Polycomb group proteins, including PHF19, play important roles in regulating cell fate determination and could be potential therapeutic targets for myeloid leukemia treatment. PHF19 depletion reduces cell proliferation and promotes leukemia cell differentiation, with its homolog MTF2 partially compensating for its effects in specific gene targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Sneha S. Varghese, Sangeeta Dhawan
Summary: Pancreatic beta-cells play a crucial role in regulating glucose homeostasis, and dysregulation of PRC-dependent epigenetic control is associated with beta-cell failure in diabetes. This review explores the multifaceted contributions of PRC modules in beta-cell specification, maintenance, and adaptation, as well as their interaction with signaling pathways. It also highlights the translational relevance of understanding the epigenetic regulation of beta-cell homeostasis in the context of diabetes and insulinomas.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Developmental Biology
Tyler J. Butsch, Olga Dubuisson, Alyssa E. Johnson, K. Adam Bohnert
Summary: Valosin-containing protein (VCP) plays an important role in regulating protein homeostasis by binding and extracting ubiquitylated cargo. It is not well understood how VCP functions in germline development, especially in males. Using the Drosophila male germline as a model system, researchers found that VCP translocates from the cytosol to the nucleus during germ cell differentiation and promotes spermatocyte gene expression by downregulating a repressive histone modification.
Review
Plant Sciences
Qingwen Shen, Yisheng Lin, Yingbo Li, Guifeng Wang
Summary: Plants have evolved sophisticated regulatory networks using epigenetic codes like H3K27me3 to adapt to fluctuating environments. Polycomb complexes PRC2 and PRC1 play essential roles in gene repression mediated by H3K27me3, with recent studies uncovering new players in this process. Understanding the dynamics of H3K27me3 in plants is crucial for studying plant adaptation to environmental stresses.
Article
Biology
Sean Akira Montgomery, Tetsuya Hisanaga, Nan Wang, Elin Axelsson, Svetlana Akimcheva, Milos Sramek, Chang Liu, Frederic Berger
Summary: This study investigates gene dosage control in the short-lived diploid embryo of the plant Marchantia polymorpha. It reveals that paternal chromosomes are repressed throughout embryogenesis, resulting in functional haploidy. The findings demonstrate the importance of maintaining haploid gene dosage through genomic imprinting during embryonic development.
Review
Genetics & Heredity
Bhuvanadas Sreeshma, Arikketh Devi
Summary: Cancer is a leading cause of death worldwide, with approximately 10 million deaths reported in the World Health Organization's 2020 report. Epigenetics, which involves heritable phenotype alterations beyond DNA changes, plays a crucial role in the development of human cancers. The Enhancer of Zeste Homologue2 (EZH2) has been identified as a key catalytic subunit involved in several essential activities, including embryogenesis, and its dysregulation contributes to the onset and metastasis of various cancers. Jumonji AT Rich Interacting Domain2 (JARID2), another important nuclear factor, has significant coordination with the PRC2 family. This review focuses on discussing the role and mechanism of EZH2 and the important contribution of JARID2 in human cancers.
Article
Genetics & Heredity
Susanne Voigt, Christin Froschauer
Summary: Environmental temperature can affect epigenetic regulation and gene expression in the fruit fly Drosophila melanogaster. Genes regulated by the Polycomb group show higher expression at lower temperatures, and this regulation is correlated with temperature-sensitive histone modifications. Differences in temperature sensitivity were also observed between flies adapted to temperate and tropical climates.
Review
Plant Sciences
Lea Faivre, Daniel Schubert
Summary: Chromatin is important for transcriptional regulation, and the histone modifications H3K4me3 and H3K27me3 are usually described as mutually exclusive activator and repressor. However, recent studies show that these marks can co-exist, forming a distinctive chromatin state called bivalency. The role of bivalency in transcriptional regulation remains unclear, but it is proposed to maintain transcriptional plasticity and prevent irreversible silencing of target genes. This review explores the potential factors involved in bivalency and highlights techniques for further study.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Cell Biology
Joyce Taylor-Papadimitriou, Joy M. Burchell
Summary: This review focuses on the role of PcG and TrxG complexes in the epigenetic regulation of gene expression and discusses the regulation of suppressive and active marks by methylases and demethylases. Mutations in histone methylases and demethylases in cancer can lead to repression of genes or activation of oncogenes.
Editorial Material
Cell Biology
Neil P. Blackledge, Robert J. Klose
Summary: The Polycomb repressive system regulates gene expression and development through chromatin. The study by Cohen and colleagues in Genes & Development demonstrates that cooperation between PRC1 and PRC2 enables stable repression of non-epidermal transcription factors, preventing compromise of epidermal cell identity and disruption of normal skin development.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Idan Cohen, Carmit Bar, Hequn Liu, Victor J. Valdes, Dejian Zhao, Phillip M. Galbo, Jose M. Silva, Haruhiko Koseki, Deyo Zheng, Elena Ezhkova
Summary: This study on epidermal development revealed a functional redundancy between Polycomb complex 1 and PRC2, highlighting their important roles in maintaining lineage identity and gene suppression.
GENES & DEVELOPMENT
(2021)
Article
Chemistry, Multidisciplinary
Peter 't Hart, Pascal Hommen, Anais Noisier, Adrian Krzyzanowski, Darijan Schueler, Arthur T. Porfetye, Mohammad Akbarzadeh, Ingrid R. Vetter, Helene Adihou, Herbert Waldmann
Summary: Researchers have developed peptide inhibitors targeting RbAp48 protein, successfully inhibiting the interaction between RbAp48 and MTA1 with high stability. Through a structure-based design strategy, the goal of improving affinity was achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Ophthalmology
Zhongdi Chu, Jessica E. Weinstein, Ruikang K. Wang, Kathryn L. Pepple
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2020)
Article
Microbiology
Kei Haga, Khalil Ettayebi, Victoria R. Tenge, Umesh C. Karandikar, Miranda A. Lewis, Shih-Ching Lin, Frederick H. Neill, B. Vijayalakshmi Ayyar, Xi-Lei Zeng, Goran Larson, Shraddha Ramani, Robert L. Atmar, Mary K. Estes
Article
Multidisciplinary Sciences
Sarah John, Kevin Rolnick, Leslie Wilson, Silishia Wong, Russell N. Van Gelder, Kathryn L. Pepple
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Shih-Ching Lin, Lin Qu, Khalil Ettayebi, Sue E. Crawford, Sarah E. Blutt, Matthew J. Robertson, Xi-Lei Zeng, Victoria R. Tenge, B. Vijayalakshmi Ayyar, Umesh C. Karandikar, Xiaomin Yu, Cristian Coarfa, Robert L. Atmar, Sasirekha Ramani, Mary K. Estes
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Editorial Material
Biotechnology & Applied Microbiology
Ying Kai Chan, Kathryn L. Pepple
Article
Engineering, Biomedical
Ganesh Swaminathan, Nabiollah Kamyabi, Hannah E. Carter, Anubama Rajan, Umesh Karandikar, Zachary K. Criss, Noah F. Shroyer, Matthew J. Robertson, Cristian Coarfa, Chenlin Huang, Tate E. Shannon, Madeleine Tadros, Mary K. Estes, Anthony W. Maresso, K. Jane Grande-Allen
Summary: This study demonstrated that human intestinal enteroids cultured on hydrogel scaffolds of different stiffness exhibited altered interactions with enteric bacteria, with softer hydrogels promoting the formation of larger aggregates. The platform offers a more biomimetic model for studying enteric diseases.
ACTA BIOMATERIALIA
(2021)
Article
Ophthalmology
K. Matthew McKay, Nicholas Apostolopoulos, Mohammad Dahrouj, Huy V. Nguyen, Amit Reddy, Marian Blazes, Megan Lacy, Kathryn L. Pepple, Aaron Y. Lee, Cecilia S. Lee
Summary: This study aimed to evaluate the uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same EHR system. The results showed perfect agreement among 5 centers for 52 out of 54 uveitis-related diagnostic terms queried within the Epic EHR.
JAMA OPHTHALMOLOGY
(2021)
Article
Ophthalmology
K. Matthew Mckay, Zhongdi Chu, Joon-Bom Kim, Alex Legocki, Xiao Zhou, Meng Tian, Marion R. Munk, Ruikang K. Wang, Kathryn L. Pepple
Summary: This study validated a custom algorithm for automated identification and quantification of clinically relevant inflammatory choriocapillaris lesions. The algorithm demonstrated good agreement with human graders and outperformed them in reproducibility. Automated lesion delineation could support the development of objective and quantitative biomarkers for disease activity in patients with posterior uveitis.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Francesco Pichi, Ester Carreno Salas, Carlos Pavesio, Alastair K. Denniston, Dilraj S. Grewal, Gabor Deak, Moncef Khairallah, Matilde Ruiz-Cruz, Joao Rafael de Oliveira Dias, Alfredo Adan, Tomas Burke, Alessandro Invernizzi, Ariel Schlaen, Meng Tian, Aniruddha Kishandutt Agarwal, William R. Tucker, H. Nida Sen, Phoebe Lin, Lyndell L. Lim, Kathryn L. Pepple, Marion R. Munk
Summary: This study establishes consensus recommendations for reporting OCTA findings in uveitis, which can serve as guidance for routine clinical care and clinical trials.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Multidisciplinary Sciences
Sarah John, Oliver H. Bell, Leslie Wilson, David A. Copland, Kathryn L. Pepple
Summary: Uveitis encompasses a range of conditions characterized by intraocular inflammation, with etiology typically classified as infectious or autoimmune. The PMU mouse model, utilizing immunization with mycobacterial extract, provides a useful tool for studying chronic ocular inflammation following mTB infection and evaluating new anti-inflammatory therapies.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Ophthalmology
Kathryn L. Pepple, Sarah John, Leslie Wilson, Victoria Wang, Russell N. Van Gelder
Summary: This study investigated the impact of prior systemic Mycobacterium tuberculosis (Mtb) infection on uveitis. It was found that prior infection exacerbated ocular inflammation and amplified Th17 and Th1 immune responses through the local production of cytokines and chemokines. Mice lacking mature T and B cells showed a weaker response to infection.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Ophthalmology
Douglas A. Jabs, Elizabeth A. Sugar, Alyce E. Burke, Michael M. Altaweel, James P. Dunn, Sapna Gangaputra, John H. Kempen, Kathryn L. Pepple, Richard J. Stawell, Janet T. Holbrook
Summary: This study evaluated the rate of cataract surgery, risk factors, and outcomes in patients with intermediate, posterior, and panuveitis treated with systemic corticosteroids and immunosuppression. The results showed a substantial long-term risk of cataract surgery in these patients. Visual acuity outcomes after cataract surgery were generally good.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Benjamin J. Steren, Philina Yee, Paola A. Rivera, Shu Feng, Kathryn Pepple, Ninani Kombo
Summary: This study examines the gender trends in ophthalmology primary practice areas and finds that the number of women in ophthalmology subspecialty practice has steadily increased over the past 30 years. While men and women specialize at the same rate, there are significant differences in the types of ophthalmology practiced by each gender.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Gayathri Tummala, Adam Crain, Jessica Rowlan, Kathryn L. Pepple
Summary: The intravitreal injection of AAV in mice results in mild clinically evident inflammation that tends to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remains elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Alex T. Legocki, Emily M. Zepeda, Thomas B. Gillette, Laura E. Grant, Ayesha Shariff, Phanith Touch, Aaron Y. Lee, Leona Ding, Marcela M. Estrada, Kristina Tarczy-Hornoch, Cecilia S. Lee, Dennis E. Mayock, Kathryn L. Pepple, Michelle T. Cabrera
OPHTHALMOLOGY RETINA
(2020)