Epigenetics & DNA Methylation

By: Kaitlyn Fonzi & Briana Barkdull

What Is Epigenetics?

Are we enslaved to our genes we inherit, or can we break free with epigenetic change?

Definitions

– Epi-: Greek root meaning upon, over, or above– Epigenome: a system whereby individual gene sequences (stretches of

DNA) could be turned on or off or made to function at higher or lower levels

– Epigenetics: modifications of the genome, heritable during cell division, that do not involve a change in the DNA sequence

– DNA Methylation*: the addition of a methyl group to cytosine to convert it to 5-methylcytosine• *occurs at CpG sites, where cytosine (C) lies next to guanine (G).

The CpG sites are in regions near the promoters of genes. These regions are known as CpG islands. The state of methylation of CpG islands is critical to both gene activity and gene expression.

– Gene Promoters: a segment of DNA usually occurring upstream from a gene coding region and acting as a controlling element in the expression of that gene

– CpG: indicates that cytosine (C) and guanine (G) are connected by a phosphodiester bond

– Phosphodiester Bond: a bond between two sugar groups and a phosphate group linking two nucleotides together

How Can You 'Turn Off' Genes?• Methylation

– Enzymes attach CH3 bundles to the beginning of the DNA strand

The same place proteins attach to activate the geneThis blockage of the CH3 results in the gene being “turned off”

Known as Methylation CH3 bundle arrangement can change throughout lifetime

Affected by lifestyle choicesEmbryonic Development: CH3 bundles can be set permanently

Mother’s choices vital to baby’s genetic welfareChromatin modification

Alteration of chromatin structure alters gene expressionAttachment of various chemical groups to histones causes this

Is Your DNA Controlled by Nature or Nurture?

• Nature: You DO inherit your DNA as a combination from both your parents• Nurture: Our day-to-day lives can influence epigenetic changes• Transgenerational Epigenetic Inheritance

– Various behavior and health conditions are due to inherited epigenetic changes

– Ex: water fleas• Due to heavy predator laden environment, fleas have developed

strong spines– Children inherit this too

• Puts evolution in a new light– Jean-Baptiste Lamarck

» Projected that the environment gives rise to changes in animals

What makes the epigenome change?

– Nutrition• shortages or excesses of food during adolescence leads to risk of obesity, diabetes, and

early puberty• during times of famine the P-generation may have an epigenetic shift where their needs

for certain nutrients are increased– if this is passed to their offspring, in time of surplus, the F1 may become overly-

nourished and develop health risks– This also occurrs if the P generation is overly-nourished and their offspring then live

in famine; they would be less likely to handle smaller portions– Parenting

• mother rats that infrequently groom and nurse their pups rear anxious offspring– this alters genes controlling the production of stress hormones– nature's way of preparing young for a potentially dangerous environment

• fathers affect epingenome as well– crop fungicide vinclozolin can cause susceptibility to cancer and kidney defects– mice fed with cocaine passed on memory failure to three generations

» all epigenetic changes passed on through Dad• suicide victims: in parts of the hippocampus, the part of the brain that affects mood,

scientists found that genes had been switched off– 1/5 suicide victims was abused as a child

Cancer Epigenetics Takes Center Stage

– Originally thought that methylation in cancer was an epiphenomenon, meaning that it was random and arose after the cancer did, not playing a role in the formation of cancerous cells.

– Differs from general genetics• reversible• position effects (act over larger distances than intended)• high frequency of mutations

– Gene silencing: essentially turning on and off genes– Hypermethylation leads to silencing of tumor suppressor genes– Loss of imprinting (LOI)-loss of normal pattern of expression of a

specific parent allele, in cancer it can lead to the activation of the growth-promoting imprinted genes

– Microsatellite Instability (MSI)-form of genetic instability found in patients with hereditary colon cancer (caused by defects in DNA mismatch repair)• MSI occurs more frequently in non-familial cases, but do not appear

to have a mismatch repair defect

Cancer Epigenetics Takes Center Stage• What distinguishes a cancer patient from a non-cancer patient?

– Boveri (father of cancer genetics) described a generalized disturbance of chromatin as the distinguishing factor• since chromatin had yet to be revealed, he based this upon

widespread disruption of chromosomal organization and nuclear structure

– Recent studies have utilized this information with the more current knowledge of chromatin to suggest that imprinting and methylation may both be bound to the assembly of DNA into organized structues (i.e. chromatin - chromosomes)

– It is possible for two genetically identical organisms to exhibit differing physical traits, such as one with cancer and one without, because of epigenetic alterations [RED BOX]

Pros vs. Cons of Epigenetics

Stem cells have recently become of interest to scientists studying epigenetics. Why do you think this is? And what would be some advantages and repercussions of them utilizing stem cells in this

way?

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