Living and Adapting to Its Own Habitat - Building the Most Complex Structure on Earth - page 207

From Where Does the Epigenetic Information for DNA
Methylation Come?
DNA methylation, the addition of a methyl (CH 3 ) group to a cytosine or adenine
ring in the DNA molecule, is responsible for the gene imprinting and inactivation of
the X chromosome. It is also involved in cell differentiation during individual devel-
opment and has a pivotal role in establishing gene expression patterns for each cell
type. Methylation is conserved during the cell division so that the epigenetic marks
serve daughter cells to “remember,” maintain, and transmit in future generations the
parental cell type. DNA methylation is reversible under the influence of chroma-
tin structure, but it also may induce the methylation of histones ( Meaney and Szyf,
2005a ).
DNA must be methylated at strictly determined sites, “where it is needed,” to
perform its function in gene imprinting, otherwise, reproduction and development
would be impossible. This suggests that information is used for methylating the right
base out of billions of bases of the DNA molecule. Obviously, this information is
different from the information for protein biosynthesis; hence, it comes from sources
that are external to DNA itself.
Let us begin with an example of a phenomenon where the flow of information
for DNA methylation may be followed upstream to what seems to be the genera-
tor of that information in response to a social stimulus. The example shows how an
early life epigenetic reprogramming, without any change in genetic information, may
switch the offspring between two alternative behaviors.
According to the level of licking and grooming (LG) of the puppies during the
first postnatal week, rat mothers display high- or low-LG behavior and they transmit
this trait to the offspring. In general, low-LG rat mothers and their offspring are more
fearful in response to stress compared to high-LG mothers. Rat puppies of high-LG
mothers that experience the affectionate maternal care during the first week of neo-
natal life, as adults, tend to show the same high-LG behavior to their own offspring.
When during the first week of life, the puppies of high-LG mothers are fostered to
low-LG/maltreating mothers; as adults, they display to their own offspring the low-
LG/maltreating behavior of the foster mother rather than the high-LG behavior of
the biological mother ( Meaney and Szyf, 2005a,b ). The epigenetically determined
behavior overrides the genetic behavior of the biological mother:
[I]ndividual differences in patterns of gene expression and behavior can be directly
linked to maternal care over the first week of life.
Meaney and Szyf (2005b)
At the cellular level, relevant changes in the cross-fostered offspring consist of
modification of the structure and function of the CA1 neuronal network of the hip-
pocampus, indicating that the maternal care modulates the development and function
of the hippocampus in rats ( Champagne et al., 2008 ).
At the molecular level, the offspring of both high- and low-LG mothers show
no differences at birth in the stress level and have the same methylation status in