Download Epigenetics

Epigenetics
By Katie Van Hove
DNA:
deoxyribonucleic
acid, Double Helix,
and it completely
and totally defines
everyone of our
characteristics!!!
…Kinda
Every cell in the human body has the same DNA, but they
definitely don’t all do the same thing.
This is because not every gene is expressed in each cell.
There are many opportunities to turn off and on a certain
gene, and to alter its phenotype, such things like…
DNA methylation: the attachment of methylated bases to
DNA bases after DNA synthesis almost solely at CpG nucleotides,
which regulates and suppresses gene expression and …
Histone Acetylation: the attachment of acetyl groups to the proteins
around which the DNA is coiled, making gene expression easier.
These additions turn the gene expression on and off, silencing some
genes and activating others. They do not change the DNA but they can be
inherited through epigenetic inheritance.
Genomic imprinting- the silencing of one of the parental alleles based on
whether it is inherited from the paternal or maternal parent.
●The gene encoding insulin-like growth factor II (IGF2/Igf2) is only
expressed from the allele inherited from the father
●The deletion of one of the X chromosomes in women in order to
avoid redundancy.
Cool, so what does that actually do?
During the Dutch Hunger Winter in WWII 30,000 died from famine.
From this we learned that prenatal exposure to famine has shown a direct
correlation to low birth weight, diabetes, obesity, coronary heart disease, breast
and other cancers. Also, low birth weight in the grandchildren, suggesting that
how our grandmothers ate when they were carrying our mothers affects our
epigenetics at least two generations later
Agouti mice have undergone DNA methylation changes by
insertion of an IAP element that caused changes in their coat color.
Dolly, the first cloned mammal, lived only for seven years. The short
lifespan and poor health of cloned animals is due to insufficient
reprogramming of epigenetic marks.
Two genetically identical agouti mice, one whose mother was fed a
diet with folic acid and other methyl-rich supplements during
pregnancy and one whose mother has a normal diet. The brown
mouse’s agouti gene has been shut off, whereas her genetically
identical sister is yellow and has a higher rate of obesity, diabetes, and
cancer.
Giving a pregnant mouse supplemental choline (C5H14N+O), (found in milk,
eggs, beef nuts, fish) a B complex vitamin, shows increased mental activity
and intelligence in the offspring. The mice whose mother received the
supplemental diet during late pregnancy had larger neurons with more
dendrites then those whose mother was fed the regular diet. “Choline has
been shown to activate two hippocampal proteins shown to contribute to
learning and memory” (Williams and Meck in collaboration with J.K. Blusztajn).
Supplementing a women’s diet with folic acid before and during the
pregnancy have shown to reduce the risk of a neural tube defect by
70%.
Monozygotic (identical) twins look different. they have the same
genes, but they have different epigenetics.
Cancer
Hypomethylation or
hypermethylation (too little
or too much) can cause the
activation of oncogenes (a
gene that causes the
transformation of normal
cells to tumorous cancer
cells) and/or the silencing
of tumor suppressor genes.
This, along with genetic
abnormalities contributes
to the formation of cancer
cells.
It only takes two of these LOH (loss of heterozygosity), Deletion,
Mutation (genetic causes), or DNA methylation (epigenetic) for the
cancer gene to become inactive.
The hypermethylation can be used as a marker of cancer cells because the
hypermethylation of the tumor suppresser genes only happens in cancerous
cells. Also, an epigenetic cause gives hope, because epigenetics are
reversible. If one could find the correct demethylating agent, the genes
silenced by methylation could be re-expressed.
●Vidaza is one such drug. It has shown considerable antitumoral
activity and has been approved for treatment of the pre-leukemic
disease myelodysplastic syndrome.
Epigenetics is a whole new field of exploration and
discovery that shows promise in helping find treatments
and cures for all disease, like cancer, lymphoma, and
leukemia. With more research we can unlock the delicate
nature of our cells, and who we are.
Bibliography
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Agouti mice. Dukemednews.duke.edu. 4/20/07.
www.dukemednews.org/.../detail.php&id=1125
Esteller, Manel. “The necessity of a human epigenome project.” Carcinogenesis, May
2006. Pg.1121–1125
Fairley, Peter. “Epigenetics” Technology Review; Mar/Apr 2006. P59-61,
Hugh D. Morgan, Heidi G.E. Sutherland, David I.K. Martin & Emma Whitelaw. “Epigenetic
inheritance at the agouti locus in the mouse” Nature Genetics 23. 1999. pg. 314 - 318
“Maternal Diet Interacts with Genome for Better...and Maybe Worse.” Genomelife. May
2004.
Moshe, Szyf. “Article Learning without learning reports on the research” The Economist ©
20069/23/2006, Vol. 380 Issue 8496, p89-90, 2p, 1c
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Plass, Christoph. “Cancer epigenomics.” Human molecular genetics, June 2002. pg 24792488
Qui, Jane. “Epigenetics unfinished symphony.” Nature, May 2006.
“The human epigenome.” Economist. 12/24/2005, Vol. 377 p108-108.
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www.wikipedia.com
Campbell and Reece. Biology 7th edition.