In other studies with mice, researchers successfully turned off the agouti gene that created a fat yellow phenotype. They forced two mice with the agouti gene on to have offspring that were thin and brown by feeding the mothers vitamin B12, folic acid, betaine, and choline; compounds found in prenatal vitamins (Moalem 158). Later, Dr. Moalem also describes some drugs that affect methylation and therefore affect how a gene is expressed, like in the case of azacitidine, an inhibitor of methylation (Moalem 175).
First of all, how and where does DNA methylation occur? Are the ingredients from prenatal vitamins such as vitamin B12, folic acid, betaine, and choline methyl donors or do they inhibit methylation? Find another compound that is a methyl donor. Is it commonly found in a normal person's diet? Is more methylation a good thing? Why or why not?
Katelyn Noronha, knoronh4@students.d125.org
First of all, how and where does DNA methylation occur? Are the ingredients from prenatal vitamins such as vitamin B12, folic acid, betaine, and choline methyl donors or do they inhibit methylation? Find another compound that is a methyl donor. Is it commonly found in a normal person's diet? Is more methylation a good thing? Why or why not?
Katelyn Noronha, knoronh4@students.d125.org
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ReplyDeleteDNA methylation “occurs when a compound called methyl group binds to a gene and changes the way that gene expresses itself, without changing the DNA.” (158). Methylation occurs in the DNA “at the cytosine bases of eukaryotic DNA, which are converted to 5-methylcytosine by DNA methyltransferase (DNMT) enzymes” (Phillips, T.). Also, DNA methylation is “an important epigenetic determinant in gene expression”. The regulation of the methylation correlates with the DNA stability as well as the chromosomal modifications and the development of mutations therefore an important aspect of DNA modifications. As we learned during Unit 10, DNA methylation turns off gene expression; it generally reduces transcription. However the removal of extra methyl groups can turn on some genes. Prenatal vitamins such as vitamin B12 and folic acid are methyl donors. These prenatal vitamins result in more DNA methylation. Like with the agouti gene experiment, the prenatal vitamins “flicked the agouti gene into ‘off’ position…DNA still contained [the gene] but it wasn’t expressed—chemicals had attached to the gene and suppressed its instructions” (158). The chemicals that had attached were methyl groups therefore the prenatal vitamins that were given were methyl donors.
ReplyDeleteAnother compound that is a methyl donor is B6. B6 can be found on meats, vegetables and nuts. It is common in a person’s diet. B6 is involved in transmethylation metabolic pathways which also intersect with the formation of methionine. Methylation depends on the availability of the “methyl groups from S-adenosylmethionine, which is derived from methionine”. The B6 pathway which intersects with the formation of methionine together contributes to the methyl donation. From the “Diet, Methyl Donors and DNA Methylation” article, the researchers discovered the importance of methyl donors as factors that “influence DNA methylation and gene expression”. Therefore, B6 from diet is a way to receive methyl groups.
Methylation can be a good thing or a bad depending on the situation. Relating methylation to Big Idea 1, the tumor suppressor genes are often hypermethylated and silenced in cancer cells. Therefore in this case of methylation, the methylation of the tumor suppressor genes is a selective disadvantage since this will lead to more cancer/spread of cancer, putting the person at high risk. However in another case, like with the agouti gene, the mice with the “switched-off agouti gene had significantly lower rates of cancer and diabetes” (158) showing a selective advantage over the mice with the agouti gene turned on. So methylation is “neither a good nor bad on its own---it all depends on what genes are being turned on and what genes are being turned off” (170).
Citation: Niculescu , M., & Zeisel , S. (n.d.). Diet, methyl donors and dna methylation: Interactions between dietary folate, methionine and choline. (2002). JOURNAL OF NUTRITION, 132(8), 2333s-2335s. Retrieved from http://jn.nutrition.org/content/132/8/2333S.long
Kim , Y., & , (n.d.). Nutritional epigenetics: Impact of folate deficiency on dna methylation and colon cancer susceptibility. (2005). JOURNAL OF NUTRITION, 135(11), 2703-2709. Retrieved from http://jn.nutrition.org/content/135/11/2703.full?sid=6bcfa072-9f11-44cc-be2c-ff92e84bba21
http://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070
(Hervy Ong, hong3@students.d125.org)