Twins, height
Why twins have different eye colour or one suffer from a disease and other not inspite of having
the same set of genes. Epigenetics explains the observed phenotypes to altered gene expression due to external factors.
school text books
The term ‘‘epigenetics’’ (literally means 'above the genes') was originally coined by Conrad Waddington in the 1940s to explain phenotypes produced due to interaction of genes with the environment without any alteration in the DNA sequence. Full understanding of epigenetics
is yet to be reached and hence, many definitions continue to exist. Epigenetics is most commonly defined as the study of heritable changes in gene expression or phenotype without rewriting genetic code. Epigenetic changes has been implicated in many diseases including cancer.
Research growth
Figure 1 : Graph showing growth of literature on epigenetics and cancer epigenetics. Search terms "epigenetics", "epigenetics" and "cancer" were used to find the number
Figure 1 : Graph showing growth of literature on epigenetics and cancer epigenetics. Search terms "epigenetics", "epigenetics" and "cancer" were used to find the number
of articles in Pubmed.
Figure 2 : Search volume as per Google Trends for the term "epigenetics"
Epigenetic mechanisms
Epigenetic events regulate the activities of genes without changing the DNA.
Gene expression depends on the methyl-marks attached to DNA and/or composition of chromatin. The main components of chromatin are histones around which 146 base-pairs of DNA are wound like a thread around a spool, forming a structure called nucleosome.
There are various epigenetic mechanisms that can affect the nucleosome :
There are various epigenetic mechanisms that can affect the nucleosome :
1. DNA methylation
2. Histone modifications
3. Role of microRNAs
4. Chromatin remodeling
Figure 3 : Illustration showing how epigenetic mechanisms can impact health.
Source : http://commonfund.nih.gov/epigenomics/epigeneticmechanisms.aspx
Epigenetics and Cancer
Figure 4 : Image showing a DNA molecule methylated on both strands at cytosine.
Source : Wiki
17 cancers linked to 20 genetic switches as per ENCODE project findings.
DNA methylation was the first epigenetic process to be linked with cancer. It regulates gene expression by hypermethylation, hypomethylation and loss of imprinting.
Figure 4 : Image showing a DNA molecule methylated on both strands at cytosine.
Source : Wiki
Illustration showing epigenetic alterations during oncogenesis (3)
Epigenetic drugs for treating cancer
Figure 5 : FDA approved epigenetic cancer drugs (4)
Schematic showing Epigenetic drug development (4)
Figure 5 : FDA approved epigenetic cancer drugs (4)
References
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1. Cancer epigenetics reaches mainstream oncology
Manuel Rodriguez-Paredes, Manel Esteller
Nature Medicine, 2011
2. Cancer epigenetics for the 21st century : What's next ?
Manel Esteller
Genes&Cancer, 2011
3. Cancer Epigenomics : beyond genomics
Juan Sandoval, Manel Esteller
Current Opinion in Genetics&Development, 2012
Old NID
94089
