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In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes 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. Epigenetic factors can also 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.
In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerational epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. The human epigenome, including DNA methylation and histone modification, is maintained through cell division. The epigenome is essential for normal development and cellular differentiation, enabling cells with the same genetic code to perform different functions. The human epigenome is dynamic and can be influenced by environmental factors such as diet, stress, and toxins.
Bert Vogelstein is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School and Sidney Kimmel Comprehensive Cancer Center. A pioneer in the field of cancer genomics, his studies on colorectal cancers revealed that they result from the sequential accumulation of mutations in oncogenes and tumor suppressor genes. These studies now form the paradigm for modern cancer research and provided the basis for the notion of the somatic evolution of cancer.
DNA (cytosine-5)-methyltransferase 1(Dnmt1) is an enzyme that catalyzes the transfer of methyl groups to specific CpG sites 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.
DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome.
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.
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.
An epigenetic clock is a biochemical test that can be used to measure age. The test is based on modifications that change over time and regulate how genes are expressed. Typically they can use DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules, or more recently, based on the histone code.
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.
H3K27me3 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.
Stephen Bruce Baylin is the deputy director and associate director for research at the Sidney Kimmel Comprehensive Cancer Center and Virginia and D.K. Ludwig Professor for Cancer Research and medicine and chief of cancer biology of the Johns Hopkins University School of Medicine. His research focus is epigenetics in the development of cancer, and he was one of the first researchers in this field in the 1980s.
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.
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).
H3K4me1 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the mono-methylation at the 4th lysine residue of the histone H3 protein and often associated with gene enhancers.
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.
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.
- ↑ "Technion to Award the Prestigious Harvey Prize to Three Groundbreaking Researchers in Cancer Epigenetics - Technion - Israel Institute of Technology". Technion - Israel Institute of Technology -. 2024-12-09. Retrieved 2024-12-23.
- ↑ "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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