Effect of small molecules on cell reprogramming

2017 ◽  
Vol 13 (2) ◽  
pp. 277-313 ◽  
Author(s):  
M. Baranek ◽  
A. Belter ◽  
M. Z. Naskręt-Barciszewska ◽  
M. Stobiecki ◽  
W. T. Markiewicz ◽  
...  

Small molecules cause pluripotency induction through epigenetic changes such as DNA methylation, histone modifications, RNA noncoding and chromatin remodeling.

2011 ◽  
Vol 2 (6) ◽  
pp. 459-467 ◽  
Author(s):  
Thomas Vaissière ◽  
Courtney A. Miller

AbstractEpigenetic mechanisms have emerged as a central process in learning and memory. Histone modifications and DNA methy­lation are epigenetic events that can mediate gene transcription. Interesting features of these epigenetic changes are their transient and long lasting potential. Recent advances in neuroscience suggest that DNA methylation is both dynamic and stable, mediating the formation and maintenance of memory. In this review, we will further illustrate the recent hypothesis that DNA methylation participates in the transcriptional regulation necessary for memory.


2020 ◽  
Vol 21 (17) ◽  
pp. 6217
Author(s):  
Ismael Khouly ◽  
Rosalie Salus Braun ◽  
Michelle Ordway ◽  
Bradley Eric Aouizerat ◽  
Iya Ghassib ◽  
...  

Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. IL6, IL6R, IFNG, PTGS2, SOCS1, and TNF were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.


2006 ◽  
Vol 27 (3) ◽  
pp. 949-962 ◽  
Author(s):  
Rugang Zhang ◽  
Song-tao Liu ◽  
Wei Chen ◽  
Michael Bonner ◽  
John Pehrson ◽  
...  

ABSTRACT Cellular information is encoded genetically in the DNA nucleotide sequence and epigenetically by the “histone code,” DNA methylation, and higher-order packaging of DNA into chromatin. Cells possess intricate mechanisms to sense and repair damage to DNA and the genetic code. However, nothing is known of the mechanisms, if any, that repair and/or compensate for damage to epigenetically encoded information, predicted to result from perturbation of DNA and histone modifications or other changes in chromatin structure. Here we show that primary human cells respond to a variety of small molecules that perturb DNA and histone modifications by recruiting HP1 proteins to sites of altered pericentromeric heterochromatin. This response is essential to maintain the HP1-binding kinetochore protein hMis12 at kinetochores and to suppress catastrophic mitotic defects. Recruitment of HP1 proteins to pericentromeres depends on histone H3.3 variant deposition, mediated by the HIRA histone chaperone. These data indicate that defects in pericentromeric epigenetic heterochromatin modifications initiate a dynamic HP1-dependent response that rescues pericentromeric heterochromatin function and is essential for viable progression through mitosis.


2019 ◽  
Vol 20 (14) ◽  
pp. 3478 ◽  
Author(s):  
Michal J. Dabrowski ◽  
Bartosz Wojtas

During the last two decades, several international consortia have been established to unveil the molecular background of human cancers including gliomas. As a result, a huge outbreak of new genetic and epigenetic data appeared. It was not only shown that gliomas share some specific DNA sequence aberrations, but they also present common alterations of chromatin. Many researchers have reported specific epigenetic features, such as DNA methylation and histone modifications being involved in tumor pathobiology. Unlike mutations in DNA, epigenetic changes are more global in nature. Moreover, many studies have shown an interplay between different types of epigenetic changes. Alterations in DNA methylation in gliomas are one of the best described epigenetic changes underlying human pathology. In the following work, we present the state of knowledge about global DNA methylation patterns in gliomas and their interplay with histone modifications that may affect transcription factor binding, global gene expression and chromatin conformation. Apart from summarizing the impact of global DNA methylation on glioma pathobiology, we provide an extract of key mechanisms of DNA methylation machinery.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mojgan Sheikhpour ◽  
Mobina Maleki ◽  
Maryam Ebrahimi Vargoorani ◽  
Vahid Amiri

AbstractSeveral studies show that childhood and adulthood asthma and its symptoms can be modulated through epigenetic modifications. Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications. How these changes lead to asthmatic phenotype or promote the asthma features, in particular by immune pathways regulation, is an understudied topic. Since external effects, like exposure to tobacco smoke, air pollution, and drugs, influence both asthma development and the epigenome, elucidating the role of epigenetic changes in asthma is of great importance. This review presents available evidence on the epigenetic process that drives asthma genes and pathways, with a particular focus on DNA methylation, histone methylation, and acetylation. We gathered and assessed studies conducted in this field over the past two decades. Our study examined asthma in different aspects and also shed light on the limitations and the important factors involved in the outcomes of the studies. To date, most of the studies in this area have been carried out on DNA methylation. Therefore, the need for diagnostic and therapeutic applications through this molecular process calls for more research on the histone modifications in this disease.


2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Bogdan Kolarz ◽  
Maria Majdan

Epigenetics is a field of science which describes external and environmental modifications to DNA without altering their primary sequences of nucleotides. Contrary to genetic changes, epigenetic modifications are reversible. The epigenetic changes appear as a result of the influence of external factors, such as diet or stress. Epigenetic mechanisms alter the accessibility of DNA by methylation of DNA or post-translational modifications of histones (acetylation, methylation, phosphorylation, ubiquitinqation). The extent of DNA methylation depends on the balance between DNA methyltransferases and demethylases. The main histone modifications are stimulated by K-acetyltransferases, histone deacetylases, K-metyltransferases and K-demethylases. There is proof that environmental modifications of this enzymes regulate immunological processes including autoimmunity in rheumatoid arthritis (RA). In this work we present epigenetic mechanisms involved in RA pathogenesis and a range of research presenting the possible impact of its modification in RA patients.


2020 ◽  
Vol 21 (8) ◽  
pp. 2887
Author(s):  
Justyna Mierziak ◽  
Wioleta Wojtasik ◽  
Anna Kulma ◽  
Mariusz Dziadas ◽  
Kamil Kostyn ◽  
...  

In mammalian cells, 3-hydroxybutyrate (3-HB) is not only an intermediate metabolite during the oxidation of fatty acids, but also an important signaling molecule. On the other hand, the information about the metabolism or function of this compound in plants is scarce. In our study, we show for the first time that this compound naturally occurs in flax. The expression of bacterial β-ketothiolase in flax affects expression of endogenous genes of the 3-HB biosynthesis pathway and the compound content. The increase in 3-HB content in transgenic plants or after control plants treatment with 3-HB resulted in upregulation of genes involved in chromatin remodeling. The observation that 3-HB is an endogenous activator of methyltransferase 3 (CMT3), decreased DNA methylation I (DDM1), DEMETER DNA glycosylase (DME), and an inhibitor of sirtuin 1 (SRT1) provides an example of integration of different genes in chromatin remodeling. The changes in chromatin remodeling gene expression concomitant with those involved in phenolics and the lignin biosynthesis pathway suggest potential integration of secondary metabolic status with epigenetic changes.


2019 ◽  
Vol 16 (4) ◽  
pp. 386-391 ◽  
Author(s):  
Kenneth Lundstrom

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.


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