Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.
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http://dx.doi.org/10.1016/j.cell.2021.05.039 | DOI Listing |
Hum Genomics
December 2024
Department of Clinical Neurosciences, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, 310003. Electronic address:
Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, lacking effective targeted therapies and presenting with a poor prognosis. In this study, we utilized the epigenomic landscape, TCGA database, and clinical samples to uncover the pivotal role of HJURP in TNBC. Our investigation revealed a strong correlation between elevated HJURP expression and unfavorable prognosis, metastatic progression, and late-stage of breast cancer.
View Article and Find Full Text PDFJ Exp Bot
December 2024
Centre of Plant Structural and Functional Genomics, Institute of Experimental Botany, Czech Acad Sci, Šlechtitelů 31, Olomouc 77900, Czech Republic.
Cytosine (DNA) methylation plays important roles in silencing transposable elements, plant development, genomic imprinting, stress responses, and maintenance of genome stability. To better understand the functions of this epigenetic modification, several tools have been developed to manipulate DNA methylation levels. These include mutants of DNA methylation writers and readers, targeted manipulation of locus-specific methylation, and the use of chemical inhibitors.
View Article and Find Full Text PDFCell Rep
December 2024
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Program in Development, Disease, Models, and Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.
View Article and Find Full Text PDFNat Commun
December 2024
National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China.
Although epigenetic modification has long been recognized as a vital force influencing gene regulation in plants, the dynamics of chromatin structure implicated in the intertwined transcriptional regulation of duplicated genes in polyploids have yet to be understood. Here, we document the dynamic organization of chromatin structure in two subgenomes of allotetraploid cotton (Gossypium hirsutum) by generating 3D genomic, epigenomic and transcriptomic datasets from 12 major tissues/developmental stages covering the life cycle. We systematically identify a subset of genes that are closely associated with specific tissue functions.
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