scholarly journals CpGislandEVO: A Database and Genome Browser for Comparative Evolutionary Genomics of CpG Islands

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Guillermo Barturen ◽  
Stefanie Geisen ◽  
Francisco Dios ◽  
E. J. Maarten Hamberg ◽  
Michael Hackenberg ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Cpg Islands ◽  
Sequence Divergence ◽  
Aberrant Methylation ◽  
Biological Processes ◽  
Orthologous Genes ◽  
Promoter Regions ◽  
Nucleotide Substitutions ◽  
Health And Disease

Hypomethylated, CpG-rich DNA segments (CpG islands, CGIs) are epigenome markers involved in key biological processes. Aberrant methylation is implicated in the appearance of several disorders as cancer, immunodeficiency, or centromere instability. Furthermore, methylation differences at promoter regions between human and chimpanzee strongly associate with genes involved in neurological/psychological disorders and cancers. Therefore, the evolutionary comparative analyses of CGIs can provide insights on the functional role of these epigenome markers in both health and disease. Given the lack of specific tools, we developedCpGislandEVO. Briefly, we first compile a database of statistically significant CGIs for the best assembled mammalian genome sequences available to date. Second, by means of a coupled browser front-end, we focus on the CGIs overlapping orthologous genes extracted fromOrthoDB, thus ensuring the comparison between CGIs located on truly homologous genome segments. This allows comparing the main compositional features between homologous CGIs. Finally, to facilitate nucleotide comparisons, we lifted genome coordinates between assemblies from different species, which enables the analysis of sequence divergence by direct count of nucleotide substitutions and indels occurring between homologous CGIs. The resultingCpGislandEVOdatabase, linking together CGIs and single-cytosine DNA methylation data from several mammalian species, is freely available at our website.

scholarly journals Histone Modifying Enzymes in Gynaecological Cancers

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 816
Author(s):  
Priya Ramarao-Milne ◽  
Olga Kondrashova ◽  
Sinead Barry ◽  
John D. Hooper ◽  
Jason S. Lee ◽  
...  
Keyword(s):  
Genome Instability ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Driver Mutations ◽  
Promoter Regions ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Cancer Types ◽  
Histone Modifying Enzymes

Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome instability and histone modifications. Histones are a major determinant of chromosomal conformation and stability, and unlike DNA methylation, which is generally associated with gene silencing, are amenable to post-translational modifications that induce facultative chromatin regions, or condensed transcriptionally silent regions that decondense resulting in global alteration of gene expression. In comparison, other components, crucial to the manipulation of chromatin dynamics, such as histone modifying enzymes, are not as well-studied. Inhibitors targeting DNA modifying enzymes, particularly histone modifying enzymes represent a potential cancer treatment. Due to the ability of epigenetic therapies to target multiple pathways simultaneously, tumours with complex mutational landscapes affected by multiple driver mutations may be most amenable to this type of inhibitor. Interrogation of the actionable landscape of different gynaecological cancer types has revealed that some patients have biomarkers which indicate potential sensitivity to epigenetic inhibitors. In this review we describe the role of epigenetics in gynaecological cancers and highlight how it may exploited for treatment.

scholarly journals Epigenetic Regulation of miR-92a and TET2 and Their Association in Non-Hodgkin Lymphoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther K. Elliott ◽  
Lloyd N. Hopkins ◽  
Robert Hensen ◽  
Heidi G. Sutherland ◽  
Larisa M. Haupt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Target Genes ◽  
Cpg Islands ◽  
Mature Mirnas ◽  
Tumour Suppressor Genes ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Non Hodgkin Lymphoma

MicroRNAs (miRNAs) are well known for their ability to regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. In various cancers, miRNAs regulate gene expression by altering the epigenetic status of candidate genes that are implicated in various difficult to treat haematological malignancies such as non-Hodgkin lymphoma by acting as either oncogenes or tumour suppressor genes. Cellular and circulating miRNA biomarkers could also be directly utilised as disease markers for diagnosis and monitoring of non-Hodgkin lymphoma (NHL); however, the role of DNA methylation in miRNA expression regulation in NHL requires further scientific inquiry. In this study, we investigated the methylation levels of CpGs in CpG islands spanning the promoter regions of the miR-17–92 cluster host gene and the TET2 gene and correlated them with the expression levels of TET2 mRNA and miR-92a-3p and miR-92a-5p mature miRNAs in NHL cell lines, tumour samples, and the whole blood gDNA of an NHL case control cohort. Increased expression of both miR-92a-3p and miR-92a-5p and aberrant expression of TET2 was observed in NHL cell lines and tumour tissues, as well as disparate levels of dysfunctional promoter CGI methylation. Both miR-92a and TET2 may play a concerted role in NHL malignancy and disease pathogenesis.

The Salivary miRNome: A Promising Biomarker of Disease

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Tomei ◽  
Harshitha Shobha Manjunath ◽  
Selvasankar Murugesan ◽  
Souhaila Al Khodor
Keyword(s):  
Current Knowledge ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Disease Pathogenesis ◽  
Technical Aspects ◽  
Recent Developments ◽  
Health And Disease ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids, and hence can serve as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling and highlighting the applicability of miRNA screening to clinical practice.

The role of Galactose in human health and disease

Open Medicine ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. 409-419 ◽  
Author(s):  
Muhammad Manwar Hussain ◽  
Mukhtarul Hassan ◽  
Noor Shaik ◽  
Zeeshan Iqbal
Keyword(s):  
Human Health ◽  
Cellular Signaling ◽  
Biological Processes ◽  
Microbial Adhesion ◽  
Wide Range ◽  
Health And Disease ◽  
Stereochemical Properties ◽  
Specific Sugar

AbstractAccording to the universal biological findings, cellular bodies are covered with an intense coating of glycans. Diversity of glycan chains, linked to lipids and proteins is due to isomeric and conformational modifications of various sugar residues, giving rise to unique carbohydrate structures with a wide range of sequences and anomeric configurations. Proteins and lipids, carrying specific sugar residues (like Galactose) with particular stereochemical properties (sequence, anomery and linkages) are involved in broad spectrums of biological processes, including intercellular and intracellular interactions, microbial adhesion and cellular signaling. By studying the role of specific seterochemical features of galactose (Gal), we have improved our understanding about the normal physiology and diseases in human bodies.

scholarly journals Comparative Analysis of Super-enhancers Across Mammals Reveals Their High Function Conservation

2020 ◽  
Author(s):  
Yanling Peng ◽  
Yubo Zhang
Keyword(s):  
Cell Types ◽  
Regulatory Elements ◽  
Biological Processes ◽  
Orthologous Sequence ◽  
Orthologous Genes ◽  
Promoter Regions ◽  
Cell Tissue ◽  
Intergenic Regions ◽  
Regulation Function ◽  
And Function

Abstract BackgroundSuper-enhancers (SEs) are key positive regulatory elements in defining cells/tissues identity in mammals, yet their similarities and differences of sequence and function across mammals have been poor studied. To allow sequence and function comparison across mammalian SEs, we employ H3K27ac ChIP-seq data to six cell types/tissues across human, pig, and mouse, which represent different lineages of mammals in the evolutionary tree.ResultsOverall, a median of 848 human SEs, 888 pig SEs and 503 mouse SEs are identified across cells/tissues. These SEs are largely distributed in promoter regions for human (91.9% in median) and mouse (63.4% in median), while mostly in distal intergenic regions for pig (66.1% in median). Extremely higher unique orthologous SEs frequency (91.6%~92.1%) has been detected for the same cell/tissue across species. Consistently, their overlapping rates are very low for the same cell/tissue across species (0.1%~0.5%). For the SE-associated orthologous genes, they also show high unique frequency for species (63.3%~83.9%) and low overlapping rates (0.8%~1.3%) at inter-species comparison. However, orthologous SEs function comparisons across species have shown similar biological processes related to cells/tissues identity in the top 15 significant enriched terms for the same cell/tissue. Meanwhile, common core transcription factors that determine cells/tissues identity are determined for the same cell/tissue across mammals.ConclusionsThis study highlights the differences of SEs genomic distribution across mammals. It reveals low orthologous sequence overlapping but high function conservation of SEs across mammals. It would improve our understanding of regulation function cis-regulatory elements in mammals.

scholarly journals TBIO-21. Lnc-TALC PROMOTES O6-METHYLGUANINE-DNA METHYLTRANSFERASE EXPRESSION VIA REGULATING THE C-MET PATHWAY BY COMPETITIVELY BINDING WITH miR-20b-3p

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii470-iii470
Author(s):  
Pengfei Wu ◽  
Jinquan Cai ◽  
Qun Chen
Keyword(s):  
Dna Methyltransferase ◽  
Noncoding Rnas ◽  
Therapeutic Resistance ◽  
Biological Processes ◽  
Promoter Regions ◽  
Methylguanine Dna Methyltransferase ◽  
Phosphorylated Akt ◽  
Clinical Benefits ◽  
Glioblastoma Recurrence

Abstract Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance. However, the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance, we induce TMZ resistant GBM cells, perform a lncRNA microarray of the parental and TMZ-resistant cells, and find an unreported lncRNA in GBM, lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence), correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore, lnc-TALC increased MGMT expression by mediating the acetylation of H3K9, H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients, lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.

Silencing of Peroxiredoxin 2 and Aberrant Methylation of 33 CpG Islands in Putative Promoter Regions in Human Malignant Melanomas

2006 ◽  
Vol 66 (12) ◽  
pp. 6080-6086 ◽  
Author(s):  
Junichi Furuta ◽  
Yoshimasa Nobeyama ◽  
Yoshihiro Umebayashi ◽  
Fujio Otsuka ◽  
Kanako Kikuchi ◽  
...  
Keyword(s):  
Cpg Islands ◽  
Aberrant Methylation ◽  
Promoter Regions ◽  
Putative Promoter ◽  
Peroxiredoxin 2 ◽  
Malignant Melanomas

scholarly journals MicroRNAs: Promising New Antiangiogenic Targets in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sandra Gallach ◽  
Silvia Calabuig-Fariñas ◽  
Eloisa Jantus-Lewintre ◽  
Carlos Camps
Keyword(s):  
Cell Types ◽  
Biological Processes ◽  
Tumour Angiogenesis ◽  
Proliferation And Apoptosis ◽  
Sequence Complementarity ◽  
Specific Proteins ◽  
Health And Disease ◽  
Multiple Cell ◽  
Non Coding Rnas

MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulators of signalling pathways in multiple cell types including endothelial and perivascular cells. This review summarises the role of miRNAs in tumour angiogenesis and their potential implications as therapeutic targets in cancer.

scholarly journals Genetics, Molecular Control and Clinical Relevance of Habituation Learning

2022 ◽  
Author(s):  
Laura E.R. Blok ◽  
Marina Boon ◽  
Boyd van Reijmersdal ◽  
Kira D. Höffler ◽  
Michaela Fenckova ◽  
...  
Keyword(s):  
Animal Models ◽  
Cognitive Processing ◽  
Neurodevelopmental Disorders ◽  
Information Overload ◽  
Sensory Information ◽  
Biological Processes ◽  
Molecular Control ◽  
Regulatory Pathways ◽  
Health And Disease

Habituation, the most ancient and fundamental form of learning, manifests already before birth. Neuroscientists have been fascinated for decades by its function as a firewall protecting our brains from sensory information overload and its indispensability for higher cognitive processing. Evidence that habituation learning is affected in autism and related monogenic neurodevelopmental syndromes and their animal models has exponentially grown, but the potential of this convergence to advance both fields is still largely unexploited.In this review, we provide a systematic overview of the genes that to date have been demonstrated to underlie habituation across species. We describe the biological processes they converge on, and highlight core regulatory pathways and repurposable drugs that may alleviate the habituation deficits associated with their dysregulation. We also summarize currently used habituation paradigms and extract the most important arguments from literature that support the crucial role of habituation for cognition in health and disease. We conclude that habituation is a powerful tool to overcome current bottlenecks in research, diagnostics and treatment of neurodevelopmental disorders.

DNA methylation events in transcription factors and gene expression changes in colon cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1593-1610
Author(s):  
Anna Díez-Villanueva ◽  
Rebeca Sanz-Pamplona ◽  
Robert Carreras-Torres ◽  
Ferran Moratalla-Navarro ◽  
M Henar Alonso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Colon Cancer ◽  
Transcription Factors ◽  
Target Genes ◽  
Linear Models ◽  
Cpg Islands ◽  
Promoter Regions ◽  
Differential Gene

Aim: Gain insight about the role of DNA methylation in the malignant growth of colon cancer. Patients & methods: Methylation and gene expression from 90 adjacent-tumor paired tissues and 48 healthy tissues were analyzed. Tumor genes whose change in expression was explained by changes in methylation were identified using linear models adjusted for tumor stromal content. Results: No differences in methylation were found between adjacent and healthy tissues, but clear differences were found between adjacent and tumor samples. We identified hypermethylated CpG islands located in promoter regions that drive differential gene expression of transcription factors and their target genes. Conclusion: Changes in methylation of a few genes provoke important changes in gene expression, by expanding the signal through transcription activation/repression.

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