Scientific Colloquium
January 28, 2011
ANDREW
FEINBERG
Director, Center for Epigenetics
King Fahd Professor of Medicine,
Molecular Biology & Genetics, and Oncology
Johns Hopkins University School
of Medicine
"Epigenetics: What You Might not
Want to Know, but Might Need to Know if You Want to Go to Mars"
Epigenetics is the study of
information, heritable during cell division, other than the DNA
sequence itself, such as DNA methylation, a covalent modification of
cytosine. DNAm is an attractive target for epidemiological study,
because it is easily measured in archived samples from pre-existing
large patient cohorts. It is now well established from gene-specific
studies that epigenetic alterations are important in cancer, and linked
to oncogene activation, tumor suppressor gene silencing, and
chromosomal instability. We have been taking an integrated approach to
catalyze the generalization of gene-specific to genomic epigenetics,
and to advance the focus in this field from cancer to common disease
generally. Doing this requires an integration of new conceptual,
technological, epidemiological and statistical approaches.
Our past work on cancer epigenetics has informed these general studies
in surprising ways. For example, a conundrum in common disease research
is the missing heritability by GWAS studies, and yet a role for
epigenetics has not been generally accepted because it has not been
clear how epigenetic marks could be transmitted in a Lamarckian manner
over many generations to allow selection. However, we have proposed
that epigenetic variation influenced by genetic variants, both
stochastic and nonrandom, could help to mediate complex traits.
Consistent with this idea, we have identified developmentally important
sites of stochastic epigenetic variation in the genome and shown that
they are stably linked to important traits such as body mass index.
This same idea of stochastic epigenetic variation has also influenced
our studies of the cancer epigenome, with some surprising results
regarding common mechanisms for altered DNA methylation in cancer, as
well as for chromatin organization, with immediate translational
implications.
Recent work from our laboratory has identified chromatin modifications
that might mediate DNA damage in response to injury. This work could
have direct bearing on chemoprotection and even correction of radiation
damage during space flight.