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In biology, epigenetics are stable heritable traits that cannot be explained by changes in DNA sequence, and the study of a type of stable change in cell function that does not involve a change to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.
DNA (cytosine-5)-methyltransferase 1 is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. In humans, it is encoded by the DNMT1 gene. DNMT1 forms part of the family of DNA methyltransferase enzymes, which consists primarily of DNMT1, DNMT3A, and DNMT3B.
Victor E. Velculescu is a Professor of Oncology and Co-Director of Cancer Biology at Johns Hopkins University School of Medicine. He is internationally known for his discoveries in genomics and cancer research.
Computational epigenetics uses statistical methods and mathematical modelling in epigenetic research. Due to the recent explosion of epigenome datasets, computational methods play an increasing role in all areas of epigenetic research.
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.
Manel Esteller graduated in medicine from the University of Barcelona in 1992, where he also obtained his doctorate, specializing in the molecular genetics of endometrial carcinoma, in 1996. He was an invited researcher at the School of Biological and Medical Sciences at the University of St Andrews, Scotland, during which time his research interests focused on the molecular genetics of inherited breast cancer.
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.
Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal and human behavior. It seeks to explain how nurture shapes nature, where nature refers to biological heredity and nurture refers to virtually everything that occurs during the life-span. Behavioral epigenetics attempts to provide a framework for understanding how the expression of genes is influenced by experiences and the environment to produce individual differences in behaviour, cognition, personality, and mental health.
Ali Shilatifard is an American biochemist/molecular biologist, the Robert Francis Furchgott Professor and chairman of the department of biochemistry and molecular genetics, and the director of the Simpson Query Institute for Epigenetics at the Northwestern University Feinberg School of Medicine. He has served as a senior editor for the journal Science, and currently serves as the Editor for Science's open access journal Science Advances. Research in Shilatifard's lab focuses on the cause of childhood leukemia through chromosomal translocations, the role of ELL in this process, and the discovery of the Super Elongation Complex as being a central complex linking MLL translocations into a diverse number of genes to leukemic pathogenesis. He is an elected fellow of the American Association for the Advancement of Science (AAAS), and elected member of American Academy of Arts & Sciences (AAA&S).
An epigenetic clock is a biochemical test that can be used to measure age. The test is based on DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules.
Nessa Carey is a British biologist working in the field of molecular biology and biotechnology. She is International Director of the technology transfer organization PraxisUnico and a visiting professor at Imperial College London.
An epigenome-wide association study (EWAS) is an examination of a genome-wide set of quantifiable epigenetic marks, such as DNA methylation, in different individuals to derive associations between epigenetic variation and a particular identifiable phenotype/trait. When patterns change such as DNA methylation at specific loci, discriminating the phenotypically affected cases from control individuals, this is considered an indication that epigenetic perturbation has taken place that is associated, causally or consequentially, with the phenotype.
CpG island hypermethylation is a phenomenon that is important for the regulation of gene expression in cancer cells, as an epigenetic control aberration responsible for gene inactivation. Hypermethylation of CpG islands has been described in almost every type of tumor.
Professor Susan J. Clark is an Australian biomedical researcher in epigenetics of development and cancer. She was elected a Fellow of the Australian Academy of Science in 2015, and is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and Research Director and Head of Genomics and Epigenetics Division at the Garvan Institute of Medical Research. Clark developed the first method for bisulphite sequencing for DNA methylation analysis and used it to establish that the methylation machinery of mammalian cells is capable of both maintenance and de novo methylation at CpNpG sites and showed is inheritable. Clark's research has advanced understanding of the role of DNA methylation, non-coding RNA and microRNA in embryogenesis, reprogramming, stem cell development and cancer and has led to the identification of epigenomic biomarkers in cancer. Clark is a founding member of the International Human Epigenome Consortium (IHEC) and President of the Australian Epigenetics Alliance (AEpiA).
Human epigenome is the complete set of structural modifications of chromatin and chemical modifications of histones and nucleotides. These modifications affect according to cellular type and development status. Various studies show that epigenome depends on exogenous factors.
Alberto Bardelli is an Italian geneticist and cancer researcher, expert in the field of precision medicine. He is a full professor of histology at the Department of Oncology, University of Turin and Scientific Director of IFOM, the AIRC Institute of Molecular Oncology.
Axel Schumacher, is a German epigenetics researcher. He invented the first microarray technologies for epigenetic biomarker discovery, developed the ‘epigenetic theory of aging’ with his research leading to the worldwide first proof of whole genome epigenetic abnormalities in Alzheimer's disease.
Andrea Baccarelli is an Italian American epigeneticist and clinical endocrinologist, best known for his academic contributions in the field of epigenetics, mitochondriomics, and computational epigenomics, with a research focus on investigating the impact of environmental exposures on human health. He serves as Professor and Chair of the Department of Environmental Health Sciences at the Columbia University Mailman School of Public Health.
References
- 1 2 3 "Andrew Paul Feinberg, M.D., M.P.H., Professor of Medicine".
- 1 2 Feinberg, Andrew (2009). "Interview: Professor Andrew Feinberg speaks to Epigenomics". Epigenomics. 1 (1): 25–7. doi:10.2217/epi.09.8. PMID 22122634.
- ↑ Feinberg, Andrew (2014). "DNA methylation in cancer: Three decades of discovery". Genome Medicine. 6 (5): 36. doi: 10.1186/gm553 . PMC 4062051 . PMID 25031622.
- ↑ "Past Recipients". Association for Molecular Pathology. Retrieved 2023-04-12.
- ↑ "Andrew P. Feinberg". scholar.google.com. Retrieved 2021-05-18.
- ↑ "Highly Cited Researchers". publons.com. Retrieved 2021-05-18.
- ↑ "Highly Cited Researchers". publons.com. Retrieved 2021-05-18.
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