Epigenetics is the study of heritable gene expression and phenotype that is not due directly to genome nucleotide sequence, rather the machinery that controls the expression of genes. A primary way that expression is controlled is through methylation of histones (the protein cores that DNA encircles for organization and to create super coiled nucleosomes, the state that the majority of DNA maintains throughout cellular life.) While DNA is coiled tightly around histones it remains in a "dormant" state where replication and transcription is minimal. To maintain this state histones are methlylated, but once demethylated the DNA begins to uncoil from around the histones allowing transcription machinery to access the unraveled DNA and the genes it contains.
Genetic methylation has been observed for many years, such as in gene imprinting and X chromosome inactivation. Although these methylations are known, the cause is not and they appear to be relatively permanent since conception and before. Not until recently was it discovered that methylation can occur after birth, and actually affected by and effecting behavioral cues. It was reported in a study comparing rat pups that grow to be either nervous or calm and happy...
When mother rats lived in a relatively calm and plentiful area they are known to groom and nurse their pups more often, and these pups in turn grow to be calm and nurturing. The opposite is also true, an unsafe poor area causes mothers to nurture and groom their pups less and the pups turn into nervous adults. When viewing the physiological differences it appears that the calm pups had more glucocorticoid (GC) receptors, therefore binding the glucocorticoid that is released for a sympathetic response (fight or flight). By binding the GC a negative feedback loop is activated that results in fewer glucocorticoids, and therefore allows the rat to return into a calmer state, the more receptors the quicker the return to homeostasis.
So why do these calmer rats have more GC receptors in the first place? Well quite simply because the gene is transcribed and then translated into proteins more often, and this is due to the demethylated state of the GC receptors region of the DNA.
Genetic methylation has been observed for many years, such as in gene imprinting and X chromosome inactivation. Although these methylations are known, the cause is not and they appear to be relatively permanent since conception and before. Not until recently was it discovered that methylation can occur after birth, and actually affected by and effecting behavioral cues. It was reported in a study comparing rat pups that grow to be either nervous or calm and happy...
When mother rats lived in a relatively calm and plentiful area they are known to groom and nurse their pups more often, and these pups in turn grow to be calm and nurturing. The opposite is also true, an unsafe poor area causes mothers to nurture and groom their pups less and the pups turn into nervous adults. When viewing the physiological differences it appears that the calm pups had more glucocorticoid (GC) receptors, therefore binding the glucocorticoid that is released for a sympathetic response (fight or flight). By binding the GC a negative feedback loop is activated that results in fewer glucocorticoids, and therefore allows the rat to return into a calmer state, the more receptors the quicker the return to homeostasis.
So why do these calmer rats have more GC receptors in the first place? Well quite simply because the gene is transcribed and then translated into proteins more often, and this is due to the demethylated state of the GC receptors region of the DNA.
This "opening" of the DNA is due to the nurturing the pup receives from its mother, and can even be simulated in nervous pups by injecting "demethylaters".
Through epigenetics heritable traits can be adjusted quickly, within generations, and with no mutation of the DNA sequence. Phenotypes can even be caused by the simple application of attention....
REFERENCES
http://learn.genetics.utah.edu/content/epigenetics/rats/
Thompson and Thompson Genetics in Medicine by Robert Nuusbaum et al
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