Mapping of the human
genome has set the scientific stage for sequels. Enter
the epigenome, which joins the transcriptome, proteome,
and metabolome to comprise next acts. Epigenomics
focuses on how heritable modification of DNA or DNA
packaging proteins can have profound effects on gene
expression. As research continues to move downstream
from genes to their tributaries, efforts are
increasing to develop epigenetically-effective drugs
and methylation-based biomarkers.
DNA methylation refers
to the chemical modification of DNA by the addition of
methyl groups. The Human Epigenome Project* seeks to
catalog all of the sites of methylation in the human
genome in all major tissues, and has now done so in 12
different tissues for chromosomes 6, 20, and 22, as
reported in the December issue of Nature Genetics.
Says Matthew Guenther
of the Whitehead Institute for Biomedical Research,
the human epigenome project picks up where the human
genome project left off. "By analogy, the human
genome project revealed a myriad of musical
instruments (i.e., genes and genetic elements) at our
disposal," says Guenther. "The epigenome
project (through DNA methylation and histone
methylation studies) will allow us to see how the cell
creates a symphony from those instruments (and
importantly, will allow us to know when an instrument
has gone out of tune)."
DNA methylation can
affect the expression of nearby genes, usually
silencing them, and is potentially an important factor
in the development of some cancers when it occurs
aberrantly. That makes methylation profiling an
important tool for cancer biologists. "As an
extension of the epigenome project, oncologists may be
able to tailor drug treatments based on a patient’s
epigenetic profile," notes Guenther.
Initially, the
information will be applied to understanding how
distinct methylation patterns influence gene
transcription programs in different cell types.
"It allows us to begin to unveil the epigenetic
‘portraits’ of normal cells versus tumor
cells," says Guenther. "Defining the
epigenetic signatures coincident with differentiation
or proliferation will give us a blueprint to more
intelligently combat diseases such as cancer."
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