CRISPR-mediated promoter de/methylation technologies for gene regulation

Sung, Chang Kyoo; Yim, Hyungshin

doi:10.1007/s12272-020-01257-8

Cited by 10 publications

(6 citation statements)

References 70 publications

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“…The CRISPR module can be used as a site-specific demethylation tool by combining the specific DNA-binding ability of inactivated 'dead' cas9 (dCas9) with demethylase, such as TET1 or TDG. Quite a few targeted demethylation studies have been published using CRISPR-dCas9 systems [189][190][191][192]. Generally, CRISPR-dCas9-TET1CD fusion proteins are paired with sgRNAs that have programmable 20 nucleotide sequences homologous to the target loci (Figure 1B).…”

Section: Site-specific Dna-binding Domainsmentioning

confidence: 99%

Targeted DNA Demethylation: Vectors, Effectors and Perspectives

Yano

Fedulov

2023

Biomedicines

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Aberrant DNA hypermethylation at regulatory cis-elements of particular genes is seen in a plethora of pathological conditions including cardiovascular, neurological, immunological, gastrointestinal and renal diseases, as well as in cancer, diabetes and others. Thus, approaches for experimental and therapeutic DNA demethylation have a great potential to demonstrate mechanistic importance, and even causality of epigenetic alterations, and may open novel avenues to epigenetic cures. However, existing methods based on DNA methyltransferase inhibitors that elicit genome-wide demethylation are not suitable for treatment of diseases with specific epimutations and provide a limited experimental value. Therefore, gene-specific epigenetic editing is a critical approach for epigenetic re-activation of silenced genes. Site-specific demethylation can be achieved by utilizing sequence-dependent DNA-binding molecules such as zinc finger protein array (ZFA), transcription activator-like effector (TALE) and clustered regularly interspaced short palindromic repeat-associated dead Cas9 (CRISPR/dCas9). Synthetic proteins, where these DNA-binding domains are fused with the DNA demethylases such as ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG) enzymes, successfully induced or enhanced transcriptional responsiveness at targeted loci. However, a number of challenges, including the dependence on transgenesis for delivery of the fusion constructs, remain issues to be solved. In this review, we detail current and potential approaches to gene-specific DNA demethylation as a novel epigenetic editing-based therapeutic strategy.

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Section: Site-specific Dna-binding Domainsmentioning

confidence: 99%

Targeted DNA Demethylation: Vectors, Effectors and Perspectives

Yano

Fedulov

2023

Biomedicines

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“…Some examples of epigenetic drugs with successful clinical use for the treatment of hematologic malignancies are DNA methylation transferase (DNMT) inhibitors (5-azacytidine and decitabine). Similarly, inhibitors of DNMT, histone acetyl transferase (HAT), and histone deacetylase (HDAC), enzymes involved in methylation and histone acetylation, as well as CRISPR-mediated methylation or demethylation of specific genes [ 198 ], are promising targets to be pursued [ 199 ]. Continued exploration of epigenetic drugs is warranted with the means to avoid off-target negative effects.…”

Section: Future Directions For Researchmentioning

confidence: 99%

Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum

Duff

Krolick

Mahmoud

et al. 2023

JCM

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Chronic pain is highly prevalent in the pediatric population. Many factors are involved in the transition from acute to chronic pain. Currently, there are conceptual models proposed, but they lack a mechanistically sound integrated theory considering the stages of child development. Objective biomarkers are critically needed for the diagnosis, risk stratification, and prognosis of the pathological stages of pain chronification. In this article, we summarize the current evidence on mechanisms and biomarkers of acute to chronic pain transitions in infants and children through the developmental lens. The goal is to identify gaps and outline future directions for basic and clinical research toward a developmentally informed theory of pain chronification in the pediatric population. At the outset, the importance of objective biomarkers for chronification of pain in children is outlined, followed by a summary of the current evidence on the mechanisms of acute to chronic pain transition in adults, in order to contrast with the developmental mechanisms of pain chronification in the pediatric population. Evidence is presented to show that chronic pain may have its origin from insults early in life, which prime the child for the development of chronic pain in later life. Furthermore, available genetic, epigenetic, psychophysical, electrophysiological, neuroimaging, neuroimmune, and sex mechanisms are described in infants and older children. In conclusion, future directions are discussed with a focus on research gaps, translational and clinical implications. Utilization of developmental mechanisms framework to inform clinical decision-making and strategies for prevention and management of acute to chronic pain transitions in children, is highlighted.

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“…CRISPR-based epigenome editing technologies can also provide the best way to treat various types of human cancers. These technologies are very effective in regulating gene expression without changing the DNA sequence so they can be used to treat cancers in which tumour suppresser genes and oncogenes have been silenced due to the methylation of their promoters [93]. These techniques can also be used effectively in agronomy to regulate the expression of different genes e.g., expression of A. thaliana stable epiallele FWA and CACTA1 transposon has been controlled by demethylating their methylated region using a fusion of human demethylase Ten-Eleven Translocation1 (TET1cd) and artificial zinc finger (ZF).…”

Section: Latest Advancements In Epigenetics Concerning Epiallelesmentioning

confidence: 99%

Role of DNA Methylation and Epialleles in Eukaryotes

Jadoon

Naz

Rashid

et al. 2021

PPASB

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Epialleles that emerge due to methylation variation in genetically identical individuals are gaining more interest due to their involvement in physiological and pathological processes. These are also important for transgenerational epigenetic inheritance and evolution. Both stable and metastable epialleles have their importance because of their contribution to the alteration of gene expression that may lead to useful traits or diseases. The main aim of this work lies in a comparative study between stable and metastable epialleles and the latest advancements that are helpful for the interpretation and analysis of DNA methylation and epialleles. However, there is so much to discover and understand because of the inadequate knowledge about methylomes of species as well as the naturally occurring epialleles in the wild. We will get more opportunities to apply this knowledge if we have a complete understanding of methylomes and epialleles and their contribution towards the normal functioning of an organism.

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CRISPR-mediated promoter de/methylation technologies for gene regulation

Cited by 10 publications

References 70 publications

Targeted DNA Demethylation: Vectors, Effectors and Perspectives

Targeted DNA Demethylation: Vectors, Effectors and Perspectives

Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum

Role of DNA Methylation and Epialleles in Eukaryotes

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