Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Molecular Tools for Epigenetic Engineering
share announcement

Molecular Tools for Epigenetic Engineering

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular Genetics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 7876

Special Issue Editors

Dr. Alexey V. Fedulov

E-Mail Website
Guest Editor
Department of Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA
Interests: epigenetic engineering; immunology; asthma; inflammation; environmental particles
Dr. Naohiro Yano

E-Mail Website
Guest Editor
Department of Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA
Interests: epigenetic engineering; immunology; protein purification; molecular biology

Special Issue Information

Dear Colleagues,

Epigenetic engineering is an exciting, cutting-edge area of research related to the modification of epigenetic marks at specific sites, which allows the targeted modulation of gene expression.

The exciting paradigm of epigenetics that ‘genes are not your destiny’ has taken a novel turn with the development of epigenetic engineering approaches to selectively manipulate the status (e.g., promoter methylation) and thus the function (transcription) of genes. This methodology can resolve two major obstacles in health research. First, epidemiological data robustly show correlation between epigenetic changes and a plethora of divergent diseases, but it has been impossible to demonstrate causality. Second, methods do not exist to exploit the power of epigenetic regulation for direct therapeutic benefit.

The discovery and characterization of molecular tools for editing the epigenome thus has promise to bring new experimental and therapeutic approaches.

This Special Issue aims to increase the awareness of epigenetic engineering and of its mechanistic and therapeutic potential, and to illuminate novel types of gene-specific epigenetically acting constructs. We invite articles on all types of experimental systems successful in modifying DNA methylation marks; the manipulation of methylation, acetylation and other histone modifications; and on all other instruments for epigenetic engineering. We are also interested in reports of the successful packaging and delivery of such constructs into cells—particularly if cell-specific.

Dr. Alexey V. Fedulov
Dr. Naohiro Yano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epigenetic engineering
  • epigenetic editing
  • targeted demethylation
  • gene-specific DNA methylation editing
  • DNMT
  • TDG
  • TET
  • histone mimics
  • fusion proteins
  • zinc finger arrays
  • dCAS9
  • gRNA
  • CRISPR

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 1710 KiB  
Article
Functional Validation of the Putative Oncogenic Activity of PLAU
by Federica Sarno, Désirée Goubert, Emilie Logie, Martijn G. S. Rutten, Mihaly Koncz, Christophe Deben, Anita E. Niemarkt, Lucia Altucci, Pernette J. Verschure, Antal Kiss, Wim Vanden Berghe and Marianne G. Rots
Biomedicines 2023, 11(1), 102; https://doi.org/10.3390/biomedicines11010102 - 30 Dec 2022
Cited by 1 | Viewed by 2234
Abstract
Plasminogen activator, urokinase (PLAU) is involved in cell migration, proliferation and tissue remodeling. PLAU upregulation is associated with an increase in aggressiveness, metastasis, and invasion of several cancer types, including breast cancer. In patients, this translates into decreased sensitivity to hormonal [...] Read more.
Plasminogen activator, urokinase (PLAU) is involved in cell migration, proliferation and tissue remodeling. PLAU upregulation is associated with an increase in aggressiveness, metastasis, and invasion of several cancer types, including breast cancer. In patients, this translates into decreased sensitivity to hormonal treatment, and poor prognosis. These clinical findings have led to the examination of PLAU as a biomarker for predicting breast cancer prognosis and therapy responses. In this study, we investigated the functional ability of PLAU to act as an oncogene in breast cancers by modulating its expression using CRISPR-deactivated Cas9 (CRISPR-dCas9) tools. Different effector domains (e.g., transcription modulators (VP64, KRAB)) alone or in combination with epigenetic writers (DNMT3A/3L, MSssI) were fused to dCas9 and targeted to the PLAU promoter. In MDA-MB-231 cells characterized by high PLAU expression downregulation of PLAU expression by CRISPR-dCas9-DNMT3A/3L-KRAB, resulted in decreased cell proliferation. Conversely, CRISPR-dCas9-VP64 induced PLAU upregulation in low PLAU expressing MCF-7 cells and significantly increased aggressiveness and invasion. In conclusion, modulation of PLAU expression affected metastatic related properties of breast cancer cells, thus further validating its oncogenic activity in breast cancer cells. Full article
(This article belongs to the Special Issue Molecular Tools for Epigenetic Engineering)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 1854 KiB  
Review
Targeted DNA Demethylation: Vectors, Effectors and Perspectives
by Naohiro Yano and Alexey V. Fedulov
Biomedicines 2023, 11(5), 1334; https://doi.org/10.3390/biomedicines11051334 - 30 Apr 2023
Cited by 3 | Viewed by 2988
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Molecular Tools for Epigenetic Engineering)
►▼ Show Figures

Figure 1

14 pages, 1126 KiB  
Review
Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
by Daniel M. Sapozhnikov and Moshe Szyf
Biomedicines 2023, 11(5), 1238; https://doi.org/10.3390/biomedicines11051238 - 22 Apr 2023
Cited by 3 | Viewed by 2231
Abstract
As advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable [...] Read more.
As advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology—specifically the risks involved in the introduction of epigenetic enzymes—and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing. Full article
(This article belongs to the Special Issue Molecular Tools for Epigenetic Engineering)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop