scholarly journals Non-CpG Methylation Revised

Epigenomes ◽  
2018 ◽  
Vol 2 (4) ◽  
pp. 22 ◽  
Author(s):  
Andrea Fuso
Keyword(s):  
Dna Methylation ◽  
Biological Activity ◽  
Cpg Methylation ◽  
Human Diseases ◽  
Biologically Relevant ◽  
Scientific Papers ◽  
A Minor

Textbook and scientific papers addressing DNA methylation usually still cite “DNA methylation occurs at CpG cytosines”. Methylation at cytosines outside the CpG nucleotide, the so-called “non-CpG methylation”, is usually considered a minor and not biologically relevant process. However, the technical improvements and additional studies in epigenetics have demonstrated that non-CpG methylation is present with frequency higher than previously thought and retains biological activity, potentially relevant to the understanding and the treatment of human diseases.

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
One Pot ◽  
Biologically Relevant ◽  
Cross Coupling Reactions ◽  
Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

Isatin: A Scaffold with Innumerable Biodiversity

2020 ◽  
Vol 20 ◽  
Author(s):  
Priyobrata Nath ◽  
Agnish Mukherjee ◽  
Sougata Mukherjee ◽  
Sabyasachi Banerjee ◽  
Samarpita Das ◽  
...  
Keyword(s):  
Biological Effects ◽  
Scientific Information ◽  
Research Work ◽  
Chemical Properties ◽  
Industrial Applications ◽  
Biologically Relevant ◽  
Extensive Information ◽  
Relevant Compound ◽  
A Minor ◽  
Clinical Conditions

: Isatin is an endogenous and a significant category of fused heterocyclic component, widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains indole nucleus having both lactam and keto moiety which while being a part of a molecular framework exerted several biological effects, viz.; antimicrobial, antitubercular, anticonvulsant, anticancer etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged to be a drug. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure Activity Relationships study thus developed through a gamut of scientific information indicates the importance of mostly electron withdrawing groups, halogens, nitro, alkoxy and to a minor extent groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at position 2 and 3 sometimes become insignificant as fusion with a heterocycle at those position resulted in a biologically relevant compound.

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

scholarly journals CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giovanni Scala ◽  
Antonio Federico ◽  
Dario Greco
Keyword(s):  
Dna Methylation ◽  
Motif Discovery ◽  
Cpg Methylation ◽  
Functional Interpretation ◽  
Dna Motifs ◽  
Molecular Alterations ◽  
Link Type ◽  
Dna Motif ◽  
Quantitative Manner ◽  
Dna Motif Discovery

Abstract Background The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.

scholarly journals Crucial Players for Inter-Organelle Communication: PI5P4Ks and Their Lipid Product PI-4,5-P2 Come to the Surface

2022 ◽  
Vol 9 ◽  
Author(s):  
Archna Ravi ◽  
Lavinia Palamiuc ◽  
Brooke M. Emerling
Keyword(s):  
Stress Response ◽  
Human Diseases ◽  
Type Ii ◽  
Metabolic Homeostasis ◽  
Cellular Homeostasis ◽  
Evolutionarily Conserved ◽  
Lipid Product ◽  
Canonical Type ◽  
Organelle Communication ◽  
A Minor

While organelles are individual compartments with specialized functions, it is becoming clear that organellar communication is essential for maintaining cellular homeostasis. This cooperation is carried out by various interactions taking place on the membranes of organelles. The membranes themselves contain a multitude of proteins and lipids that mediate these connections and one such class of molecules facilitating these relations are the phospholipids. There are several phospholipids, but the focus of this perspective is on a minor group called the phosphoinositides and specifically, phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2). This phosphoinositide, on intracellular membranes, is largely generated by the non-canonical Type II PIPKs, namely, Phosphotidylinositol-5-phosphate-4-kinases (PI5P4Ks). These evolutionarily conserved enzymes are emerging as key stress response players in cells. Further, PI5P4Ks have been shown to modulate pathways by regulating organelle crosstalk, revealing roles in preserving metabolic homeostasis. Here we will attempt to summarize the functions of the PI5P4Ks and their product PI-4,5-P2 in facilitating inter-organelle communication and how they impact cellular health as well as their relevance to human diseases.

scholarly journals Intergenerational epigenetic inheritance in reef-building corals

2018 ◽  
Author(s):  
Yi Jin Liew ◽  
Emily J. Howells ◽  
Xin Wang ◽  
Craig T. Michell ◽  
John A. Burt ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intergenerational Transmission ◽  
Epigenetic Inheritance ◽  
Cpg Methylation ◽  
Epigenetic Mechanisms ◽  
Transgenerational Inheritance ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

scholarly journals Genome-Wide DNA Methylation Analysis during Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yangyang Cao ◽  
Haoqing Yang ◽  
Luyuan Jin ◽  
Juan Du ◽  
Zhipeng Fan
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Biological Process ◽  
Cpg Methylation ◽  
Genome Wide ◽  
Marrow Mesenchymal Stem Cells ◽  
Go Terms

Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising candidates in cell-based therapy for the regeneration of damaged bone tissues that are either incurable or intractable due to the insufficiency of current therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and that this differentiation is regulated by some specific patterns of epigenetic modifications, such as DNA methylation. However, the potential role of DNA methylation modification in BMSC osteogenic differentiation is unclear. In this study, we performed a genome-wide study of DNA methylation between the noninduced and induced osteogenic differentiation of BMSCs at day 7. We found that the majority of cytosines in a CpG context were methylated in induced BMSCs. Our results also revealed that, along with the induced osteogenic differentiation in BMSCs, the average genomic methylation levels and CpG methylation in transcriptional factor regions (TFs) were increased, the CpG methylation level of various genomic elements was mainly in the medium-high methylation section, and CpG methylation levels in the repeat element had highly methylated levels. The GO analysis of differentially methylated region- (DMR-) associated genes (DMGs) showed that GO terms, including cytoskeletal protein binding (included in Molecular Function GO terms), skeletal development (included in Biological Process GO terms), mesenchymal cell differentiation (included in Biological Process GO terms), and stem cell differentiation (included in Biological Process), were enriched in the hypermethylated DMGs. Then, the KEGG analysis results showed that the WNT pathway, inositol phosphate metabolism pathway, and cocaine addiction pathway were more correlative with the DMRs during the induced osteogenic differentiation in BMSCs. In conclusion, this study revealed the difference of methylated levels during the noninduced and induced osteogenic differentiation of BMSCs and provided useful information for future works to characterize the important function of epigenetic mechanisms on BMSCs’ differentiation.

Catecholamine Metabolites in Congenital Sensory Neuropathy with Anhydrosis

PEDIATRICS ◽  
1980 ◽  
Vol 65 (1) ◽  
pp. 154-157
Author(s):  
Walid O. Shekim ◽  
Anasseril E. Daniel ◽  
Richard L. Koresko ◽  
Harutoune Dekirmenjian
Keyword(s):  
Nervous System ◽  
Biological Activity ◽  
Inborn Error ◽  
Sensory Neuropathy ◽  
Catecholamine Metabolism ◽  
Urinary Catecholamine ◽  
Tyrosine Metabolism ◽  
Catecholamine Metabolites ◽  
Sympathetic Nervous ◽  
A Minor

Congenital sensory neuropathy with anhydrosis is a rare syndrome in childhood, characterized by disturbed thermoregulation and by absence of pain and sweating.1,2 The etiology is unknown, but researchers postulate the presence of a disorder in the function of the autonomic sympathetic nervous system.3 From among the numberous etiologies considered to play a role in the pathophysiology of the syndrome, we list a few that are relevant to this report: (1) disturbance of catecholamine metabolism,3 (2) an inborn error of metabolism involving a minor pathway of tyrosine metabolism,4 and (3) low biological activity of nerve growth factor (NGF).5 Clinicians have used urinary catecholamine metabolites in the diagnosis of the syndrome.3

scholarly journals Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development

Epigenomics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 701-713 ◽  
Author(s):  
Ali Altıntaş ◽  
Rhianna C Laker ◽  
Christian Garde ◽  
Romain Barrès ◽  
Juleen R Zierath
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Gene Ontology ◽  
Circadian Rhythms ◽  
Oscillatory Behavior ◽  
Cpg Methylation ◽  
Rhythmic Expression ◽  
Cpg Sites ◽  
Circadian Control ◽  
Insight Into

Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with Gene Ontology terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.

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