What is epigenetics?
Is the study of heritable and potentially reversible gene-expression changes that do not involve structural alterations in the DNA sequence, such as mutations. Is emerging as one of the most dynamic and vibrant biomedical areas .
Epigenetics is the study of heritable and potentially reversible gene expression changes that do not involve structural alterations. DNA sequence,such as mutations.This term was coined to describe changes that could not be explained by genetic mechanisms. These major types of epigenetic changes have been describe:DNA methylation, covalent post translational histone modification and small inhibitory RNA-mediated signaling pathways. DNA methylation is the most extensively studied epigenetic modification in humans. Epigenetic reprogramming during mammalian development
In at least two developmental stags in mammals, gametogenesis and pre-implantation development ,the DNA methylation pattern is reprogrammed genome-wide. This epigenetic reprogramming is believed to be necessary for return to pluripotency and for lineage commitment. In mammals, the genomes of mature sperm cells and egg remain highly methylated until fertilization. During pre-implantation development, a second round of demethylation takes place in the zygote, occuring at different rates in the two parental genomes. Demethylation of the paternal genome- occurs after fertilization but before cell division, it is more rapid than in the maternal genome, and involves an active mechanism. Demethylation of the maternal genome- occurs gradually over the first few cleavage divisions of the embryo, involves a passive mechanism, and is dependent on DNA replication Both the paternal and the maternal genomes are remethylated around the time of implantation.
The HGP began in 1990, it is a 13-year effort coordinated and funded by the U. S. Department of Energy and the National Institutes of Health. The Human Genome Project's goals are to identify all the 100, 000 genes in human DNA; determine the sequences of the 3 billion chemical base pairs that make up human DNA; store this information in databases; develop tools for data analysis; transfer related ...
Epigenetics and cancer
Cancer cells often show global DNA hypomethylation, a modification associated with chromosomal instability, hypermethylation at promoter CpG sites, which causes aberrant genes silencing, and disruption in the normal pattern of covalent histone modifications. The global loss of histone H4K20 trimethylation and histone H4k16 acetylation are among the frequently described changes that occur in cancer cells. (2009) Kitago- revealed, for the first time, that the mRNA for RUNX3, a tumor suppressor gene involved in several cancers, is suppressed in primary cutaneous melanoma and is further suppressed in metastatic tumors, as compared with normal tissue. (2007) Nobeyama- reported hypermethylation of the TFP12 tumor suppressor gene in 29% of the metastatic melanomas examined, but in none of their primary tumors of origin. These findings point toward the involvement of hypermethylation and gene inactivation in tumor metatesis. An epigenetic switch
By transiently activating with tamoxifen a fusion construct between the (v-Src) and the ligand-binding domain of estrogen receptor, (2009) iliopoulus- revealed that the inflamatory response initiated an epigenetic switch and, as a result, a non-transformed state. The authors subsequently identified two microRNAs,miR-21 and miR-181-b1, which are known to be involved in human cancers, and are differentially regulated as part of this positive feedback loop. The transient expression of either of these microRnas was sufficient to activate the epigenetic switch and cause transformation.
Case studies: Epigenetics & Environmental Exposures
For many years, it was erroneously assumed that, to cause cancer, a compound has to cause mutations in the double-stranded DNA, and mutation were viewed as the only way that could lead to carcinogenosis. Consequently it was assumed, equally erroneously , that a compound cannot cause cancer as long as it does not mutate the DNA. 1. Arsenic- a human carcinogen causally linked to skin, liver, lung, and bladder cancer, does not appear to be mutagenic and does not induce point mutations in standard mutagenesis assays. 2. Infectious Diseases- the human papilloma virus, hepatitis B virus, and certain helicobacter pylori strains are among the most extensively studied microorganism, causally linked, respectively, to cancer of the cervix and esophagus, liver and stomach. > Fernandez (2009) reported for the first time a dynamic methylation pattern that occurs in several double-stranded cancer-causing DNA viruses.
Breast Cancer Breast cancer is the most common cancer among women. The American cancer society estimates that in 2002 about 192, 200 new cases of breast cancer will be diagnosed among women in the U. S. alone. Breast cancer also occurs in men. An estimated 1, 500 cases will be diagnosed among men. In 2002, there will be about 40, 600 deaths from breast cancer in the United States. What is breast ...
3. Polycyclic Aromatic Hydrocarbons & Chemicals from Cigarette Smoke- one of the most extensively studied environmental toxins is tobacco smoke, a mixture of >4000 chemicals, at least 62 of which show sufficient evidence of human or animal carcinogenicity. Certain components of cigarette smoke are mutagens, but increasing numbers of studies describe epigenetic perturbations as a result of exposure. Polycyclic aromatic hydrocarbons (PAHs) are among of the most extensively studied chemicals from cigarette smoke. 4. Social and Emotional Factors- social interactions were recently linked to epigenetic changes, possibly via hormonal pathways. Several recent findings reveal that epigenetic changes could help understand the biological basis of posttraumatic stress disorder. 5. Dietary Factors- the intrauterine environment is instrumental for offspring development and perturbations during this stage may have long-lasting consequences in the adult. The effects of maternal nutritional deprivation during pregnancy on the risk of adult-onset disease are illustrated by studies from the Dutch Hunger Winter, also known as the Dutch Famine. The “Barker hypothesis,” also known as the “developmental origins of health and disease,” is concept used to describe the increased risk of developing adult-onset chronic diseases by adults exposed to unfavorable conditions during intrauterine development.
Ang, Y.S., Gaspar-Maia, A., Lemischka, I.R. and Bernstein,E.