Autoimmune diseases are enigmatic and complex, and most been associated with epigenetic changes. Epigenetics describes changes in gene expression related to environmental influences mediated by a variety of effectors that alter the three-dimensional structure of chromatin and facilitate transcription factor or repressor binding. Recent years have witnessed a dramatic change and acceleration in epigenetic editing approaches, spurred on by the discovery and later development of the CRISPR/Cas9 system as a highly modular and efficient site-specific DNA binding domain. The purpose of this article is to offer a review of epigenetic editing approaches to date, with a focus on alterations of DNA methylation, and to describe a few prominent published examples of epigenetic editing. We will also offer as an example work done by our laboratory demonstrating epigenetic editing of the FOXP3 gene in human T cells. Finally, we discuss briefly the future of epigenetic editing in autoimmune disease.
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http://dx.doi.org/10.1016/j.clim.2018.02.001 | DOI Listing |
Binding of transcription factors (TFs) at gene regulatory elements controls cellular epigenetic state and gene expression. Current genome-wide chromatin profiling approaches have inherently limited resolution, complicating assessment of TF occupancy and co-occupancy, especially at individual alleles. In this work, we introduce Accessible Chromatin by Cytosine Editing Site Sequencing with ATAC-seq (ACCESS-ATAC), which harnesses a double-stranded DNA cytosine deaminase (Ddd) enzyme to stencil TF binding locations within accessible chromatin regions.
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December 2024
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Organs Development and Epigenetics, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China.
Reproductive system diseases have become a major health challenge facing humans, so extensive investigations are needed to understand their complex pathogenesis and summarize effective treatments. In the study of reproductive diseases, mice are the most commonly used animal model. However, the cost and time required to establish mouse animal models are high.
View Article and Find Full Text PDFBiol Sex Differ
January 2025
Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events.
View Article and Find Full Text PDFMamm Genome
December 2024
ICAR-National Bureau of Animal Genetic Resources, Karnal, India.
The sustainability of livestock systems is widely acknowledged to be threatened by climate change on a worldwide scale. There are worries about the effects this phenomenon may have on the productivity and performance of native livestock species due to its influence on environmental stresses, such as the frequency and severity of unfavorable weather occurrences and the ongoing changes in the agro-ecological landscape. Among the most climatically tolerant livestock animals, goats can survive in a range of environments, from deserts to alpine areas.
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