Article
Biochemistry & Molecular Biology
Aishwarya Gurumurthy, David T. Yu, Jared R. Stees, Pamela Chamales, Ekaterina Gavrilova, Paul Wassel, Lu Li, Daniel Stribling, Jinyang Chen, Marissa Brackett, Alexander M. Ishov, Mingyi Xie, Jorg Bungert
Summary: SEs mediate high transcription levels by recruiting transcription complexes and generating eRNAs. The LCR is able to recruit transcription complexes independently from linked genes, and HS2 initiates bidirectional transcription. Integrator complex plays a role in terminating eRNA transcription and interacts downstream of LCR HS2, affecting transcription of beta-globin genes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Anil K. Panigrahi, David M. Lonard, Bert W. O'Malley
Summary: This study demonstrates the interdependence of transcription between enhancers and target promoters. The results suggest that transcriptional concurrence and coordination throughout the genome are based on the transcriptional interdependence of enhancers and promoters. The study proposes a model where enhancers and promoters are entangled in the form of enhancer-promoter contact, reside in a proteinaceous bubble, and utilize shared transcriptional resources and regulatory inputs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Matthew D. Gibbons, Yu Fang, Austin P. Spicola, Niko Linzer, Stephen M. Jones, Breanna R. Johnson, Lu Li, Mingyi Xie, Jorg Bungert
Summary: Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast recruit components of the RNA polymerase II transcription machinery. Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates enhancer RNA (eRNA), while UASs in yeast do not recruit the required transcription factor TFIIH. In both systems, Pol II is transferred from enhancers/UASs to promoters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Lilin Wan, Wenchao Li, Yuan Meng, Yue Hou, Ming Chen, Bin Xu
Summary: This review summarizes the roles and regulatory mechanisms of functional enhancers and enhancer RNAs (eRNAs) in inflammatory immune cells, non-inflammatory immune cells, inflammatory immune diseases, and tumors, and explores the potential therapeutic effects of enhancer inhibitors affecting eRNA production for diseases with inflammatory immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Le Xiong, Erik A. Tolen, Jinmi Choi, Sergiy Velychko, Livia Caizzi, Taras Velychko, Kenjiro Adachi, Caitlin M. MacCarthy, Michael Lidschreiber, Patrick Cramer, Hans R. Schoeler
Summary: The transcription factor Oct4 is essential for stem cell pluripotency, and this study investigates its functions by depleting and recovering it in embryonic stem cells. Oct4 depletion results in loss of binding to enhancers and decreased mRNA synthesis of target genes involved in maintaining pluripotency. Partial recovery of Oct4 expression increases chromatin accessibility but does not fully restore enhancer transcription. These findings suggest that Oct4 has concentration-dependent activities.
Article
Biology
Ibrahim Ahmed, Shen-Hsi Yang, Samuel Ogden, Wei Zhang, Yaoyong Li, Andrew D. Sharrocks, William C. Hahn
Summary: This article utilizes RNA-seq data and open chromatin maps to identify potential enhancer RNAs and associated enhancer regions in oesophageal adenocarcinoma. It discovers OAC-specific enhancers and uncovers new cellular pathways operative in OAC. The study also demonstrates the clinical utility of the dataset for disease stage identification and patient prognosis.
Article
Immunology
Gangqiang Guo, Huijing Wang, Xinya Tong, Lele Ye, Xinyu Shi, Su Fang, Ya Hu, Fei Han, Chaosheng Chen, Ning Ding, Bofeng Su, Xiangyang Xue, Huidi Zhang
Summary: This study investigated the transcriptional landscape and potential functions of enhancer RNAs (eRNAs) in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. The results identified SLE-specific eRNAs, which were mainly regulated by SLE-specific transcription factors, and showed their involvement in regulating SLE-related pathways. Among the candidate eRNAs, TCONS_00034326 was significantly upregulated in SLE patients and associated with SLE-relevant signaling pathways.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Zhiqiang Huang, Ning Liang, Saioa Goni, Anastasios Damdimopoulos, Cheng Wang, Raphaelle Ballaire, Jennifer Jager, Henri Niskanen, Hongya Han, Tomas Jakobsson, Adrian P. Bracken, Myriam Aouadi, Nicolas Venteclef, Minna U. Kaikkonen, Rongrong Fan, Eckardt Treuter
Summary: This study investigated the role of corepressors in enhancer activity and transcriptional regulation, showing that corepressors act antagonistically with coactivators in transcriptional control. Additionally, they found that corepressors and coactivators play opposite roles in regulating the expression of the Ccl2 gene. Depletion of the enhancer-transcribed eRNA of the Ccl2 gene in adipose tissue macrophages in mice can reduce metaflammation.
Article
Neurosciences
Sunil Bhattarai, Aparna Akella, Atish Gandhi, Ashutosh Dharap
Summary: Recent studies have shown the widespread transcription of mammalian enhancers into noncoding eRNAs, some of which play central roles in regulating gene expression during development and disease. In cerebral ischemia, the functions of eRNAs are largely unknown. This study identified stroke-induced eRNAs in the post-stroke cortex and demonstrated the involvement of eRNA in modulating post-stroke cortical brain damage, as well as sex-dependent patterns in eRNA expression that may underlie physiological differences in response to stroke between males and females.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Cell Biology
Qianhui Li, Xin Liu, Jingtao Wen, Xi Chen, Bumin Xie, Yang Zhao
Summary: With the advancement of high-throughput sequencing technology, an increasing number of non-coding RNAs have been discovered, including miRNAs, lncRNAs, circRNAs, snoRNAs, and piRNAs. The identification of eRNAs in 2010 has expanded the diversity of non-coding RNAs. eRNAs are non-coding RNA molecules transcribed from enhancer fragments of DNA cis-acting elements. Recent studies have revealed that eRNA transcription may serve as a biological marker for enhancer activity and can participate in the regulation of coding gene transcription. This review discusses the biological characteristics of eRNAs, their functions in transcriptional regulation, the factors regulating eRNA production, and the research progress of eRNAs in different diseases.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Immunology
Kazuko Miyazaki, Masaki Miyazaki
Summary: This article discusses the driving factors of cell type-specific gene expression, emphasizing the importance of the interplay between chromatin architectures and TFs in cell fate decisions and cell type-specific functions, as well as the key roles of SEs and Rag1/2 genes in adaptive immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Anirudh Pillai, Akhila Gungi, Puli Chandramouli Reddy, Sanjeev Galande
Summary: Studying cnidarians like Hydra can enhance our understanding of the evolutionary foundations underlying eumetazoan tissue development, homeostasis, and regeneration. These organisms exhibit unique regenerative potential and continuously active axial patterning, necessitating large-scale gene expression changes governed by a variety of epigenetic mechanisms within cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Teresa Romeo Luperchio, Leandros Boukas, Li Zhang, Genay Pilarowski, Jenny Jiang, Allison Kalinousky, Kasper D. Hansen, Hans T. Bjornsson
Summary: The study reveals shared epigenetic alterations in different MDEM diseases, primarily localized in gene promoters, which may disrupt gene expression and contribute to specific phenotypes, such as IgA deficiency. Joint study of MDEMs offers a systematic approach for mapping functional epigenetic variation in mammals.
Article
Biochemistry & Molecular Biology
Yujin Kang, Yea Woon Kim, Jin Kang, AeRi Kim
Summary: Histone H3K4me1 and H3K27ac have reciprocal effects on each other, with H3K4me1 affecting nucleosome eviction and H3K27ac influencing enhancer RNA transcription. The loss of H3K4me1 reduces H3K27ac at enhancers, while H3K27ac is required for eRNA transcription independently of H3K4me1.
Review
Biochemistry & Molecular Biology
Emilie Bourdonnay, Thomas Henry
Summary: Gasdermins (GSDM) are a family of proteins that play important roles in cell death, immune response, disease susceptibility, and treatment response. The expression of GSDM genes is influenced by various factors and has been associated with diseases such as asthma, inflammatory bowel disease, and cancer.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
Yuliya Voskobiynyk, Jonathan R. Roth, J. Nicholas Cochran, Travis Rush, Nancy V. N. Carullo, Jacob S. Mesina, Mohammad Waqas, Rachael M. Vollmer, Jeremy J. Day, Lori L. McMahon, Erik D. Roberson
Article
Multidisciplinary Sciences
Katherine E. Savell, Jennifer J. Tuscher, Morgan E. Zipperly, Corey G. Duke, Robert A. Phillips, Allison J. Bauman, Saakshi Thukral, Faraz A. Sultan, Nicholas A. Goska, Lara Ianov, Jeremy J. Day
Article
Neurosciences
Morgan E. Zipperly, Faraz A. Sultan, Guan-En Graham, Andrew C. Brane, Natalie A. Simpkins, Nancy V. N. Carullo, Lara Ianov, Jeremy J. Day
Summary: Exposure to drugs of abuse leads to long-lasting transcriptional and epigenetic changes in brain reward circuits, contributing to addiction. The gene Gadd45b plays a crucial role in dopamine-dependent epigenetic regulation and cocaine reward, as demonstrated through pharmacological manipulations and gene knockout experiments.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nancy V. N. Carullo, Robert A. Phillips, Rhiana C. Simon, Salomon A. Roman Soto, Jenna E. Hinds, Aaron J. Salisbury, Jasmin S. Revanna, Kendra D. Bunner, Lara Ianov, Faraz A. Sultan, Katherine E. Savell, Charles A. Gersbach, Jeremy J. Day
NUCLEIC ACIDS RESEARCH
(2020)
Article
Neurosciences
Philipp Mews, Erin S. Calipari, Jeremy Day, Mary Kay Lobo, Timothy Bredy, Ted Abel
Summary: The central goal of neuroscience research is to understand how experiences modify brain circuits for future adaptive behavior, involving complex interactions between circuit activity and gene regulation. Disruptions in this interplay are linked to debilitating psychiatric conditions, emphasizing the importance of studying how neural circuits and the epigenome cooperate to produce behavioral adaptation.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Skylar E. Davis, Jonathan R. Roth, Qays Aljabi, Ahmad R. Hakim, Katherine E. Savell, Jeremy J. Day, Andrew E. Arrant
Summary: Loss-of-function mutations in progranulin are a major genetic cause of frontotemporal dementia, with the neurotrophic and antiinflammatory effects of progranulin potentially contributing to this. The protective effects of progranulin against excitotoxicity are likely mediated through lysosomes, specifically through the autophagy-lysosomal pathway. Lysosome-targeted progranulin showed more consistent protective effects, indicating a mechanistic link between progranulin's lysosomal and neurotrophic effects.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Editorial Material
Neurosciences
Jennifer J. Tuscher, Jeremy J. Day
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Nancy V. N. Carullo, Jenna E. Hinds, Jasmin S. Revanna, Jennifer J. Tuscher, Allison J. Bauman, Jeremy J. Day
Summary: Targeted genetic and epigenetic modification is crucial in molecular neuroscience to understand gene regulatory mechanisms underlying complex behaviors. While CRISPR-based systems have revolutionized genome editing, few tools exist for cell-specific CRISPR activation in neurons. This study presents a Cre-dependent CRISPRa system with improved efficiency and specificity, providing a versatile tool for gene regulation in different model systems.
Article
Neurosciences
L. J. McMeekin, K. L. Joyce, L. M. Jenkins, B. M. Bohannon, K. D. Patel, A. S. Bohannon, A. Patel, S. N. Fox, M. S. Simmons, J. J. Day, A. Kralli, D. K. Crossman, R. M. Cowell
Summary: This study identified ERRa as necessary for normal expression of PGC-1a-dependent genes in neurons, with a strong correlation in expression between ERRa and PGC-1a in the brain. In ERRa null mice, PGC-1a-dependent genes were reduced in multiple brain regions, leading to behavioral abnormalities without severe motor impairments seen in PGC-1a null mice.
Correction
Neurosciences
L. J. McMeekin, K. L. Joyce, L. M. Jenkins, B. M. Bohannon, K. D. Patel, A. S. Bohannon, A. Patel, S. N. Fox, M. S. Simmons, J. J. Day, A. Kralli, D. K. Crossman, R. M. Cowell
Article
Cell Biology
Robert A. Phillips, Jennifer J. Tuscher, Samantha L. Black, Emma Andraka, N. Dalton Fitzgerald, Lara Ianov, Jeremy J. Day
Summary: This study comprehensively defines the molecular architecture of the ventral tegmental area (VTA) by performing single-nucleus RNA sequencing on rat VTA cells. It identifies selective markers for dopamine and combinatorial neurons, reveals expression profiles for drug receptors, and demonstrates population-specific enrichment of gene sets linked to brain disorders.
Editorial Material
Neurosciences
Jeremy J. Day, Keri Martinowich
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Jennifer Tuscher, Robert Philliips, Samantha Black, Lara Ianov, Jeremy J. Day
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Corey. G. G. Duke, Svitlana. V. V. Bach, Jasmin. S. S. Revanna, Faraz. A. A. Sultan, Nicholas. T. T. Southern, M. Natalie Davis, Nancy V. N. Carullo, Allison. J. J. Bauman, Robert. A. A. Phillips, Jeremy. J. J. Day
FRONTIERS IN GENOME EDITING
(2020)
