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| Photo credit: © WGBH Educational Foundation |
With few exceptions, namely functionally variable regions in the immune system and in disease, all of a person’s cells have the same DNA sequences and genes. Yet the variety of cells in terms of shape and function is vast. How is it that a muscle cell and a blood cell have the same genes yet do such strikingly different things?
In short, not every gene is being used or transcribed by all cell types: There are certain genes that are essential for blood cells that muscle cells don’t express (transcribe) or use. For example, genes making proteins that recognize foreign bodies would be useful for an immune blood cell but would be a waste of a muscle cell’s energy. The burgeoning fields of epigenetics and epigenomics investigate these patterns of on/off genes and what regulates their expression. Epigenomics refers to the genome-wide application of epigenetics, which generally refers more to single-gene analyses.
Where does it apply?
“Epigenetic” as an adjective refers to heritable traits that are not changes to the DNA sequence itself. Heritability can be across both cell divisions as well as trans-generational. When a fat cell replicates and both daughter cells retain fat cell traits, inheritance is referred to as divisional/replication inheritance. When offspring retain traits of their parents, the inheritance is termed trans-generational inheritance.
A famous example of such trans-generational epigenetic inheritance is the Dutch Hongerwinter. In 1944, the Dutch in areas of the Nazi-occupied Netherlands were starving as the result of a blockade. Fetuses that developed in the wombs of mothers surviving the famine showed a number of characteristic traits of nutrient deprivation themselves, including glucose sensitivity. Later biochemical analyses demonstrated epigenetic marks on genes regulating insulin-like growth factors– characteristics of nutrient deprivation– despite no change in the DNA of these genes. Further tests of second-generation offspring may show that these marks and traits acquired in response to starvation are inherited across multiple generations.
Before Darwin’s famous description of evolution by natural selection, Jean-Baptiste Lamarck proposed the idea that traits acquired by the parent can be passed down to offspring. For instance, a giraffe’s neck is long because its parents had to stretch to reach higher trees. When On the Origin of Species elegantly explained population shifts by survival, the idea of heritability of acquired traits lost popularity. The theory was further buried when Mendelian genetics demonstrated the mechanism of genetic inheritance. It has lain dormant until a recent resurgence in interest implicating epigenetics as a plausible explanation for trans-generational inheritance of acquired traits.
How does it work?
Roughly 3 meters of DNA sequence is stored inside every nucleated human cell; the condensation and packaging of the DNA sequence is essential to regulation of gene expression. In general, uncondensed genes are expressed more readily than condensed genes. Following is a discussion of the various methods by and degrees to which genes are condensed into “chromatin”– the name given to the DNA/condensing protein complex.
