Did you mean: epi genome
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Methods (San Diego, Calif.) Mar 2021The definition of epigenetics refers that molecular modifications on DNA that can regulate gene activity are independent of DNA sequence and mitotically stable. Notably,... (Review)
Review
The definition of epigenetics refers that molecular modifications on DNA that can regulate gene activity are independent of DNA sequence and mitotically stable. Notably, epigenetics studies have grown exponentially in the past few years. Recent progresses that lead to exciting discoveries and groundbreaking nature of this area demand thorough methodologies and advanced technologies to move epigenetics to the forefront of molecular biology. The most recognized epigenetic regulations are DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). This review will discuss the modern techniques that are available to detect locus-specific and genome-wide changes for all epigenetic codes. Furthermore, updated analysis of technologies, newly developed methods, recent breakthroughs and bioinformatics pipelines in epigenetic analysis will be presented. These methods, as well as many others presented in this specific issue, provide comprehensive guidelines in the area of epigenetics that facilitate further developments in this promising and rapidly developing field.
Topics: Biomedical Research; DNA Methylation; Epigenesis, Genetic; Epigenomics; Histone Code; Humans; RNA, Untranslated
PubMed: 32645449
DOI: 10.1016/j.ymeth.2020.06.022 -
Neuron Jan 2021Single-cell sequencing technologies, including transcriptomic and epigenomic assays, are transforming our understanding of the cellular building blocks of neural... (Review)
Review
Single-cell sequencing technologies, including transcriptomic and epigenomic assays, are transforming our understanding of the cellular building blocks of neural circuits. By directly measuring multiple molecular signatures in thousands to millions of individual cells, single-cell sequencing methods can comprehensively characterize the diversity of brain cell types. These measurements uncover gene regulatory mechanisms that shape cellular identity and provide insight into developmental and evolutionary relationships between brain cell populations. Single-cell sequencing data can aid the design of tools for targeted functional studies of brain circuit components, linking molecular signatures with anatomy, connectivity, morphology, and physiology. Here, we discuss the fundamental principles of single-cell transcriptome and epigenome sequencing, integrative computational analysis of the data, and key applications in neuroscience.
Topics: Brain; DNA Methylation; Epigenome; Epigenomics; Humans; Sequence Analysis, DNA; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 33412093
DOI: 10.1016/j.neuron.2020.12.010 -
Epigenetics Dec 2019Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to... (Review)
Review
Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to reprogram the epigenetic landscape in the cancer epigenome is one of the most promising target therapies in both treatment and reversibility of drug resistance. Epigenetic alterations in cancer development and progression may be the basis for the individual variation in drug response. Thus, this review focuses on the emerging area of pharmaco(epi)genomics, specifically highlighting epigenetic reprogramming during tumorigenesis and how epigenetic markers are targeted as a therapy (epidrugs) and the clinical implications of this for cancer treatment.
Topics: Animals; Antineoplastic Agents; Epigenesis, Genetic; Epigenomics; Humans; Neoplasms; Pharmacogenetics
PubMed: 31282279
DOI: 10.1080/15592294.2019.1640546 -
Nature Apr 2023Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue...
Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.
Topics: Animals; Humans; Mice; Chromatin; Epigenesis, Genetic; Epigenome; Epigenomics; Gene Expression Profiling; Gene Expression Regulation; Mammals; Transcriptome; Histones; Single-Cell Analysis; Organ Specificity; Brain; Aging
PubMed: 36922587
DOI: 10.1038/s41586-023-05795-1 -
Current Opinion in Chemical Biology Aug 2020Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the... (Review)
Review
Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced short palindromic repeat-dCas9 greatly accelerated the advancement of epigenetic editing, yielding preclinical therapeutic successes using a variety of epigenetic enzymes. Here, we review the current applications of these epigenetic editing tools in mammals and shed light on biochemical improvements that facilitate versatile applications.
Topics: Animals; CRISPR-Cas Systems; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Editing; Genome; Histone Code; Humans
PubMed: 32619853
DOI: 10.1016/j.cbpa.2020.04.020 -
Trends in Immunology Aug 2020Effective anticancer immunotherapy treatments constitute a qualitative leap in cancer management. Nonetheless, not all patients benefit from such therapies because they... (Review)
Review
Effective anticancer immunotherapy treatments constitute a qualitative leap in cancer management. Nonetheless, not all patients benefit from such therapies because they fail to achieve complete responses, suffer frequent relapses, or develop potentially life-threatening toxicities. Epigenomic signatures in immune and cancer cells appear to be accurate and promising predictors of patient outcomes with immunotherapy. In addition, combined treatments with epigenetic drugs can exploit the dynamic nature of epigenetic changes to potentially modulate responses to immunotherapy. Candidate epigenetic biomarkers may provide a rationale for patient stratification and precision medicine, thus maximizing the chances of treatment success while minimizing unwanted effects. We present a comprehensive up-to-date view of potential epigenetic biomarkers in immunotherapy and discuss their advantages over other indicators.
Topics: Combined Modality Therapy; Epigenesis, Genetic; Epigenomics; Humans; Immunotherapy; Neoplasms
PubMed: 32622854
DOI: 10.1016/j.it.2020.06.002 -
Cell Nov 2022The recent development of spatial omics methods has enabled single-cell profiling of the transcriptome and 3D genome organization with high spatial resolution. Expanding...
The recent development of spatial omics methods has enabled single-cell profiling of the transcriptome and 3D genome organization with high spatial resolution. Expanding the repertoire of spatial omics tools, a spatially resolved single-cell epigenomics method will accelerate understanding of the spatial regulation of cell and tissue functions. Here, we report a method for spatially resolved epigenomic profiling of single cells using in situ tagmentation and transcription followed by multiplexed imaging. We demonstrated the ability to profile histone modifications marking active promoters, putative enhancers, and silent promoters in individual cells, and generated high-resolution spatial atlas of hundreds of active promoters and putative enhancers in embryonic and adult mouse brains. Our results suggested putative promoter-enhancer pairs and enhancer hubs regulating developmentally important genes. We envision this approach will be generally applicable to spatial profiling of epigenetic modifications and DNA-binding proteins, advancing our understanding of how gene expression is spatiotemporally regulated by the epigenome.
Topics: Mice; Animals; Epigenomics; Histone Code; Promoter Regions, Genetic; Epigenesis, Genetic; Transcriptome; Enhancer Elements, Genetic; Chromatin
PubMed: 36272405
DOI: 10.1016/j.cell.2022.09.035 -
Cell Sep 2023Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly...
Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly understood. Here, we profile epigenomic and transcriptomic landscapes of 850,000 nuclei from prefrontal cortexes of 92 individuals with and without AD to build a map of the brain regulome, including epigenomic profiles, transcriptional regulators, co-accessibility modules, and peak-to-gene links in a cell-type-specific manner. We develop methods for multimodal integration and detecting regulatory modules using peak-to-gene linking. We show AD risk loci are enriched in microglial enhancers and for specific TFs including SPI1, ELF2, and RUNX1. We detect 9,628 cell-type-specific ATAC-QTL loci, which we integrate alongside peak-to-gene links to prioritize AD variant regulatory circuits. We report differential accessibility of regulatory modules in late AD in glia and in early AD in neurons. Strikingly, late-stage AD brains show global epigenome dysregulation indicative of epigenome erosion and cell identity loss.
Topics: Humans; Alzheimer Disease; Brain; Epigenome; Epigenomics; Gene Expression Regulation; Genome-Wide Association Study
PubMed: 37774680
DOI: 10.1016/j.cell.2023.08.040 -
ELife Apr 2022Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with...
Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of somatic cell reprogramming, which suggests full reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first "maturation phase transient reprogramming" (MPTR) method, where reprogramming factors are selectively expressed until this rejuvenation point then withdrawn. Applying MPTR to dermal fibroblasts from middle-aged donors, we found that cells temporarily lose and then reacquire their fibroblast identity, possibly as a result of epigenetic memory at enhancers and/or persistent expression of some fibroblast genes. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome was rejuvenated to a similar extent, including H3K9me3 levels and the DNA methylation ageing clock. The magnitude of rejuvenation instigated by MPTR appears substantially greater than that achieved in previous transient reprogramming protocols. In addition, MPTR fibroblasts produced youthful levels of collagen proteins, and showed partial functional rejuvenation of their migration speed. Finally, our work suggests that optimal time windows exist for rejuvenating the transcriptome and the epigenome. Overall, we demonstrate that it is possible to separate rejuvenation from complete pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
Topics: Cellular Reprogramming; DNA Methylation; Epigenome; Epigenomics; Fibroblasts; Humans; Induced Pluripotent Stem Cells; Middle Aged; Rejuvenation
PubMed: 35390271
DOI: 10.7554/eLife.71624 -
American Journal of Respiratory and... Aug 2022Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.... (Meta-Analysis)
Meta-Analysis
Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV, FVC, and FEV/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, <0.025) in relation to FEV, FVC, or FEV/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.
Topics: CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenome; Epigenomics; Genome-Wide Association Study; Humans; Infant, Newborn; Lung
PubMed: 35536696
DOI: 10.1164/rccm.202108-1907OC