Nature vs. Nurture….or….Genes vs. Environment
A Study Grant Proposal
prepared by
Amy Helms, PhD
for
Summer 2011
January 22, 2010
Nature vs. Nurture….or….Genes vs. Environment
For ages, people have wondered which matters more….nature or nurture. Recent
advances in the field of genetics are now allowing us to explore this complex question.
The inspiration for this study grant comes from a NOVA special entitled: “Ghost in Your
Genes,” which sheds light on the phenomenon of epigenetic inheritance. The prefix
“epi” comes from the Greek, meaning “over.” Thus, the term “epigenetics” means “over
the genes.” In my opinion, epigenetics is the new frontier of genetics research and
probably one the most daunting aspects of the Human Genome Project we have faced
yet.
In addition to the genes/DNA we inherit from our parents, we can also inherit so-called
“epigenetic modifications" that can occur in response to the environment. These
"modifications" are not the same as mutations (changes in the DNA sequence) but
something "extra" added to the DNA already present. This can affect the activity of the
genes...how often they are "expressed" (ON or OFF), or it can affect the amount of
expression (LESS or MORE).
These data offer a really good theory of how the environment can affect the activity of
our genes, by making changes to the regulation of the gene rather than the gene itself.
Unlike mutations (which are permanent), these changes can be temporary or
permanent.
Imagine yourself in your mother's womb. Imagine that whatever environmental
influences to which your mother is exposed, you are also exposed. If one of your genes
is modified, it affects the activity of the gene and potentially affects your development
in the womb. This could also work in the form of having a modification taken off of a
gene.
Imagine your mother in HER mother's womb (your grandmother). While your mother
was developing in the womb, so were her future eggs (and hence 1/2 of the future you).
So whatever environmental influences your grandmother was experiencing can also
affect the activity of your genes through modifications. Think of how different the
environment was when your grandmother was pregnant. For some this could be WWII,
for others it was the turn of the 20th century. These modifications can be passed down
through generations. So now your genetic makeup includes the actual genes PLUS any
changes to those genes during your lifetime.
This phenomenon has the potential to explain many of the complex health issues we
face today, like diabetes, autism, schizophrenia, etc. Scientists are always looking for
"the gene" for some disorder, but if it affects the ACTIVITY of the gene through an
outside mechanism they would be barking up the wrong tree. Even more complicated,
each person's pattern of modifications (or gene markings) are likely very different and
subject to change within their lifetime. If you think sequencing the entire human
genome was a complicated project, mapping the epigenome, as it is called, is enormous.
I believe this concept to be incredibly important, both in understanding our genetic
heritage and in understanding how the environment affects how we look and behave. I
would love to have the opportunity to weave this new information into all my classes.
I propose to complete my studies on epigenetics during the Summer session of 2011
(Summer I). A detailed study plan is included with this proposal.
Weekly Study Plan
Many of the sources I have listed are categorized as primary literature. Because this is
such a new and evolving field, it is not possible to find many books on this topic. I have
categorized my readings as either book or as journal articles.
In addition, because of the nature of scientific research, I cannot include the most
current sources one year in advance. The sources listed below are examples of what I
can find right now in the literature. Prior to beginning my studies, I will search the
primary literature again for the most up-to-date research on these topics.
Week 1
In the first week of my studies, I will read general reviews on epigenetics and the
mechanisms by which genes can be regulated by epigenetic modifications.
BOOKS
Haslberger, A, and Greler, S. Epigenetics and Human Health: Linking Hereditary,
Environmental, and Nutritional Aspects. Wiley-VCH. 2010
Pinter, B. and Meszaros, Z. Epigenetics: Mechanisms, Functions, and Human Effects.
Nova Science Pub. 2009.
JOURNAL ARTICLES
Beck S, Olek A, Walter J. From genomics to epigenomics: a loftier view of life. 1999 Nat
Biotechnol. 17(12):1144.
Goldberg, A.D., Allis, C.D., and Bernstein, E. Epigenetics: A Landscape Takes Shape. 2007
Cell 128 (4): 635-638.
Shi, Y. Taking Epigenetics Center Stage. 2007 Cell 128(4): 639-640
Pfennig, D. and Ledon-Rettig, C. The Flexible Organism. 2009 Science 325: 268-269
Dove, A. Epigenetics: The Final Frontier? 2009 Science 326:303
Week 2
During week two I will focus my studies on the role of DNA methylation in epigenetics.
BOOKS
Doerfler, W. and Bohm, P. DNA Methylation: Basic Mechanisms. Springer. 2006
JOURNAL ARTICLES
Novik KL, Nimmrich I, Genc B, Maier S, Piepenbrock C, Olek A, Beck S. Epigenomics:
genome-wide study of methylation phenomena. Curr Issues Mol Biol. 2002 Oct;4(4):11128. Review.
Tost, J. DNA methylation: an introduction to the biology and the disease-associated
changes of a promising biomarker. 2010 Mol. Biotechnology. 44(1):71-81
Estecio, MR, and Issa, JP Tackling the methylome: recent methodological advances in
genome wide methylation profiling. 2009. Genome Medicine 16:1(11):106
Bartholomei, MS. Genomic imprinting: employing and avoiding epigenetic processes.
2009. Genes and Development 23(18):2124-2133
Week 3
During week three I will focus on a second form of epigenetic regulation: chromatin
remodeling.
BOOKS
Turner, B. Chromatin and Gene Regulation: Mechanisms in Epigenetics.Wiley-Blackwell.
2002.
Workman, JL. Protein Complexes that Modify Chromatin. Current Topics in Microbiology
and Immunology. Springer. 2003.
JOURNAL ARTICLES
Racki, L.R., Yang, J.G., Naber, N., Partensky, P.D., Acevedo, A., Purcell, T.J. Cooke, R.,
Cheng, Y. and Narlikar, G.J. The chromatin remodeller ACF acts as a dimeric motor to
space nucleosomes. 2009 Nature 462(7276): 1016-1021
MacDonald, JL, and Roskams, AJ. Epigenetic regulation of nervous system development
by DNA methylation and histone deacetylation. 2009. Progress in Neurobiology 88(3):
170
Week 4
During week four I will read a variety of papers that discuss the role of these
epigenetic mechanisms in a number of different disease processes.
BOOKS
Church, D. The Genie in Your Genes: Epigenetic Medicine and the New Biology of
Intention. Elite Publishing.2007.
JOURNAL ARTICLES
Ross, SA, and Milner, JA. Epigenetic modulation and cancer: effect of metabolic
syndrome? 2007. American Journal of Clinical Nutrition 86 (3): s872-7
Karberg, S. Switching on epigenetic therapy. 2009. Cell. 139(6):1029-31
Ling, C. and Groop, L. Epigenetics: a molecular link between environmental factors and
type 2 diabetes. Diabetes 2009 58(12): 2718-25
Chen, J, Odenike, O, and Rowley, JD. Leukemogenesis: more than mutant genes. 2010.
Nature Reviews Cancer 10(1): 23-36
Handel,AE, Ebers, GC, and Ramagopalan, SV. Epigenetics: molecular mechanisms and
implications for disease. 2009. Trends in Molecular Medicine
Ganesan, A. Nolan, L, Crabb, SJ, and Packham G. Epigenetic therapy: histone acetylation,
DNA methylation, and anti-cancer drug discovery. Current Cancer Drug Targets. 9(8):
963-81.
Weller, M, Stupp, R, Reifenberger, G, Brandes, AA, van den Bent, MJ, Wick, W, and Hegi,
ME. MGMT promoter methylation in malignant gliomas: ready for personalized
medicine? 2010 Nature Reviews Neurology 6(1): 39-51
Xu, N, Azziz, R, Goodarzi, MO. Epigenetics in polycystic ovary syndrome: A pilot study of
global DNA methylation. 2009 Fertility Sterility.
Huynh, JL, and Casaccia P. Defining the chromatin landscape in demyelinating disorders.
2009. Neurobiology Disorders.
MacDonald, JL, and Roskams, AJ. Epigenetic regulation of nervous system development
by DNA methylation and histone deacetylation. 2009. Progress in Neurobiology 88(3):
170
Week 5
In the final week, I will research how nutrition and diet affect gene regulation through
epigenetic mechanisms.
BOOKS
Choi, SW, and Friso, S. Nutrients and Epigenetics. CRC press. 2009.
JOURNAL ARTICLES
Dolinoy, DC, Weidman, JR, Waterland, RA, and Jirtle, R. Maternal genistein alters coat
color and protects Aw mouse offspring from obesity by modifying the fetal epigenome.
2006. Environmental Health Perspectives.
Kussmann, M and Affolter, M. Proteomics at the center of nutrigenomics:
comprehensive molecular understanding of dietary health effects. 2009 Nutrition 25
(11-12): 1085-93
Vaquero, A. and Reinberg D. Calorie restriction and the exercise of chromatin. 2009
Genes & Development 23(16): 1849-69
Campion J, Milagro, FI, Martinez, JA. Individuality and epigenetics in obesity. 2009
Obesity Reviews 10(4): 383-92
Levin, BE. Epigenetic influences on food intake and physical activity level: review of
animal studies. 2008. Obesity (Silver Spring) Suppl. 3:S51-4
Dashwood, RH, and Ho, E.Dietary histone deacetylase inhibitors: from cells to mice to
man. 2007 Seminars in Cancer Biology 17(5): 363-9
Kirkland, JB. 2009. Niacin status impacts chromatin structure. Journal of Nutrition
139(12): 2397-401