EPIGENETICS AS A MECHANISM FOR POSTNATAL
NUTRITIONAL PROGRAMMING
One means of regulating gene expression over the long
term is epigenetics. Epigenetics refers to heritable changes
in gene transcription caused by mechanisms other than
changes in the underlying DNA sequence.Another way to
think of epigenetics is as a means of selectively utilizing
the large array of information contained within the
genome, particularly in the context of tissue specificity
and developmental timing. Epigenetic modifications to
chromatin, the functional unit of DNA and protein, affect
gene transcription by altering chromatin’s threedimensional
structure and associations with the transcription
machinery. Epigenetic modifications include
DNA methylation, which affects transcription factor
binding, and modifications to histones. Modification to
the histone proteins occur largely, but not exclusively, in
the N-terminal tail region and include acetylation and
methylation (see review by Kouzarides54) (Figure 1). The
effects of individual histone modifications on transcription
are not straightforward and provide a complex
means of regulating transcription. Generalities such as
methylation of histone H3 lysine 9 (K9) contributing to
gene inactivation, and methylation of histone H3 lysine 4
(K4) increasing gene expression, are complicated by the
compound effect of multiple modifications.
Epigenetic modulation of gene transcription, that is,
adjusting the level of expression of genes already being
transcribed, can elicit subtle changes to phenotype and
provide the “plasticity” necessary to respond to variations
in environment. The last decade has seen much interest in
the effect of prenatal events on the epigenetic characteristics
of the developing fetus. This is true of early embryogenesis
and assisted reproduction,55 late gestational
insults such as maternal hypertensive disorders,56 and
gestation-wide insults related to dietary and environmental
exposures.57,58 Based on the notion that the developing
fetus is susceptible to epigenetic changes, it is reasonable
to assume that the preterm infant is also susceptible. Prolonged
changes in gene expression in response to differing
postnatal diets are also consistent with epigenetic
modifications.
Early-life nutrition has the capacity to alter chromatin
structure and gene expression and to modulate health