Epigenetic Regulation and Its Impact for Medicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 4302

Special Issue Editor


E-Mail Website
Guest Editor
Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruska 87, Vinohrady, 10000 Prague, Czech Republic
Interests: epigenetics of human; etiopatogenesis of multifactorial diseases; immunogenetics of autoimmunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The term epigenetics was first introduced by Conrad Waddington in 1942. For half a century, its significance to gene expression, cell differentiation and heritability was unclear. However, modern technologies that emerged at the beginning of the 21st century have opened a new area of research. The epigenetic regulation of the genome allow cells to react to external signals caused by the alternation of gene activity by modifying gene expression. Epigenome controls the accessibility of DNA for transcription factors that regulate the level of gene expression. Therefore, epigenetic modifications are the collective heritable changes in phenotype caused by the processes that arise independent of primary DNA sequence.

A major driving force in epigenetics has been the development of new technology that has not only stimulated new discoveries, but also expanded this field by allowing novel discoveries only possible through the use of these tools.

Plenty of studies have focused on the identification of possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and its response to disease-modifying drugs. Non-coding RNAs have the potential to serve as such biomarkers. These molecules can easily be detected in the peripheral blood or urine.

We encourage authors to submit articles and review papers about the role of epigenetic modulation in the etiopathology, prognosis and therapy of various diseases. We believe that this Special Issue will reflect the new era of epigenetics and show its important role in modern medicine.

Dr. Marie Černá
Guest Editor

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

  • gene expression
  • DNA methylation
  • histone modifications
  • non-coding RNAs
  • biomarkers

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 2564 KiB  
Article
CBP/P300 Inhibition Impairs CD4+ T Cell Activation: Implications for Autoimmune Disorders
by Lucas Wilhelmus Picavet, Anoushka A. K. Samat, Jorg Calis, Lotte Nijhuis, Rianne Scholman, Michal Mokry, David F. Tough, Rabinder K. Prinjha, Sebastiaan J. Vastert and Jorg van Loosdregt
Biomedicines 2024, 12(6), 1344; https://doi.org/10.3390/biomedicines12061344 - 18 Jun 2024
Viewed by 238
Abstract
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation [...] Read more.
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation of histone 3 at Lysine 27 (H3K27ac) at enhancer and promoter regions of proinflammatory cytokines, thereby increasing the expression of these genes which is essential for T cell function. Co-activators E1A binding protein P300 (P300) and CREB binding protein (CBP), collectively known as P300/CBP, are essential to facilitate H3K27 acetylation. Presently, the role of P300/CBP in human CD4+ T cells activation remains incompletely understood. To assess the function of P300/CBP in T cell activation and autoimmune disease, we utilized iCBP112, a selective inhibitor of P300/CBP, in T cells obtained from healthy controls and JIA patients. Treatment with iCBP112 suppressed T cell activation and cytokine signaling pathways, leading to reduced expression of many proinflammatory cytokines, including IL-2, IFN-γ, IL-4, and IL-17A. Moreover, P300/CBP inhibition in T cells derived from the inflamed synovium of JIA patients resulted in decreased expression of similar pathways and preferentially suppressed the expression of disease-associated genes. This study underscores the regulatory role of P300/CBP in regulating gene expression during T cell activation while offering potential insights into the pathogenesis of autoimmune diseases. Our findings indicate that P300/CBP inhibition could potentially be leveraged for the treatment of autoimmune diseases such as JIA in the future. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Show Figures

Graphical abstract

15 pages, 294 KiB  
Article
Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers
by Kyle J. Burghardt, Paul R. Burghardt, Bradley H. Howlett, Sabrina E. Dass, Brent Zahn, Ahmad A. Imam, Abdullah Mallisho, Zaher Msallaty, Berhane Seyoum and Zhengping Yi
Biomedicines 2024, 12(5), 1057; https://doi.org/10.3390/biomedicines12051057 - 10 May 2024
Viewed by 709
Abstract
Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may [...] Read more.
Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)

Review

Jump to: Research

17 pages, 734 KiB  
Review
The Importance of Sleep in Overcoming Childhood Obesity and Reshaping Epigenetics
by Erika Richter, Priyadarshni Patel, Jeganathan Ramesh Babu, Xu Wang and Thangiah Geetha
Biomedicines 2024, 12(6), 1334; https://doi.org/10.3390/biomedicines12061334 - 15 Jun 2024
Viewed by 318
Abstract
The development of childhood obesity is a complex process influenced by a combination of genetic predisposition and environmental factors, such as sleep, diet, physical activity, and socioeconomic status. Long-term solutions for decreasing the risk of childhood obesity remain elusive, despite significant advancements in [...] Read more.
The development of childhood obesity is a complex process influenced by a combination of genetic predisposition and environmental factors, such as sleep, diet, physical activity, and socioeconomic status. Long-term solutions for decreasing the risk of childhood obesity remain elusive, despite significant advancements in promoting health and well-being in school and at home. Challenges persist in areas such as adherence to interventions, addressing underlying social determinants, and individual differences in response to treatment. Over the last decade, there has been significant progress in epigenetics, along with increased curiosity in gaining insights into how sleep and lifestyle decisions impact an individual’s health. Epigenetic modifications affect the expression of genes without causing changes to the fundamental DNA sequence. In recent years, numerous research studies have explored the correlation between sleep and the epigenome, giving a better understanding of DNA methylation, histone modification, and non-coding RNAs. Although significant findings have been made about the influence of sleep on epigenetics, a notable gap exists in the literature concerning sleep-related genes specifically associated with childhood obesity. Consequently, it is crucial to delve deeper into this area to enhance our understanding. Therefore, this review primarily focuses on the connection between sleep patterns and epigenetic modifications in genes related to childhood obesity. Exploring the interplay between sleep, epigenetics, and childhood obesity can potentially contribute to improved overall health outcomes. This comprehensive review encompasses studies focusing on sleep-related genes linked to obesity. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Show Figures

Figure 1

17 pages, 1544 KiB  
Review
Therapeutic Nonsense Suppression Modalities: From Small Molecules to Nucleic Acid-Based Approaches
by Pedro Morais, Rui Zhang and Yi-Tao Yu
Biomedicines 2024, 12(6), 1284; https://doi.org/10.3390/biomedicines12061284 - 10 Jun 2024
Viewed by 608
Abstract
Nonsense mutations are genetic mutations that create premature termination codons (PTCs), leading to truncated, defective proteins in diseases such as cystic fibrosis, neurofibromatosis type 1, Dravet syndrome, Hurler syndrome, Beta thalassemia, inherited bone marrow failure syndromes, Duchenne muscular dystrophy, and even cancer. These [...] Read more.
Nonsense mutations are genetic mutations that create premature termination codons (PTCs), leading to truncated, defective proteins in diseases such as cystic fibrosis, neurofibromatosis type 1, Dravet syndrome, Hurler syndrome, Beta thalassemia, inherited bone marrow failure syndromes, Duchenne muscular dystrophy, and even cancer. These mutations can also trigger a cellular surveillance mechanism known as nonsense-mediated mRNA decay (NMD) that degrades the PTC-containing mRNA. The activation of NMD can attenuate the consequences of truncated, defective, and potentially toxic proteins in the cell. Since approximately 20% of all single-point mutations are disease-causing nonsense mutations, it is not surprising that this field has received significant attention, resulting in a remarkable advancement in recent years. In fact, since our last review on this topic, new examples of nonsense suppression approaches have been reported, namely new ways of promoting the translational readthrough of PTCs or inhibiting the NMD pathway. With this review, we update the state-of-the-art technologies in nonsense suppression, focusing on novel modalities with therapeutic potential, such as small molecules (readthrough agents, NMD inhibitors, and molecular glue degraders); antisense oligonucleotides; tRNA suppressors; ADAR-mediated RNA editing; targeted pseudouridylation; and gene/base editing. While these various modalities have significantly advanced in their development stage since our last review, each has advantages (e.g., ease of delivery and specificity) and disadvantages (manufacturing complexity and off-target effect potential), which we discuss here. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Show Figures

Figure 1

19 pages, 998 KiB  
Review
Regulation of the Function and Expression of EpCAM
by Di Xiao, Mingrui Xiong, Xin Wang, Mengqing Lyu, Hanxiang Sun, Yeting Cui, Chen Chen, Ziyu Jiang and Fan Sun
Biomedicines 2024, 12(5), 1129; https://doi.org/10.3390/biomedicines12051129 - 20 May 2024
Viewed by 726
Abstract
The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target [...] Read more.
The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target for cancer therapy. As a cell adhesion molecule, EpCAM has a crystal structure that indicates that it forms a cis-dimer first and then probably a trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), EpCAM and its proteolytic fragments are also able to regulate multiple signaling pathways, Wnt signaling in particular. Although great progress has been made, increasingly more findings have revealed the context-specific expression and function patterns of EpCAM and their regulation processes, which necessitates further studies to determine the structure, function, and expression of EpCAM under both physiological and pathological conditions, broadening its application in basic and translational cancer research. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Show Figures

Figure 1

37 pages, 3491 KiB  
Review
lncRNA Biomarkers of Glioblastoma Multiforme
by Markéta Pokorná, Marie Černá, Stergios Boussios, Saak V. Ovsepian and Valerie Bríd O’Leary
Biomedicines 2024, 12(5), 932; https://doi.org/10.3390/biomedicines12050932 - 23 Apr 2024
Viewed by 1037
Abstract
Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have [...] Read more.
Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Show Figures

Figure 1

Back to TopTop