You Are What Your Mother Ate:
The Science of Epigenetics
Daniel Lieber
Kerry Samerotte
Brian Beliveau
October 6, 2010
Today’s Lecture
Daniel Lieber
- What is epigenetics?
Kerry Samerotte
- Epigenetics and us
Brian Beliveau
- Past, present, and future
You Are What Your Mother Ate:
What is Epigenetics?
Daniel Lieber
DNA is the Source of
Heritable Information in the Cell
cell
DNA
tissue
organism cell
chromosomes
DNA sequence
Creative commons user: ynse, Wikimedia
Central Dogma
DNA is transcribed to RNA is translated to PROTEIN
DNA
Mutation
Mutation in RNA
Altered
protein
Huges, A. Connexions Project. 2003, Wikimedia Commons, Flickr
Same DNA, Different Look
• We are made up of over 200 cell types. cell
• Each cell has the same DNA!
• How can they look so different? DNA
Epigenetics!
• Genes turned on or off ?
Wikimedia Commons, ORNL.gov, Flickr: richdelux
Epigenetic Marks
DNA is transcribed to RNA is translated to PROTEIN
Epigenetic
Mark
RNA Protein
Huges, A. Connexions Project. 2003, Wikimedia Commons, Flickr
Each Cell has an Epigenetic Signature
• Epigenetic state is like a barcode:
Liver Skin Muscle
Presence of an epigenetic mark at a particular location in the DNA
Epigenetic
mark
DNA
• Epigenome = complete epigenetic state of a cell
Wikimedia Commons
Two Types of Epigenetic Marks
Chemical Protein
e.g., Methylation e.g., Histones
Methyl group Histone DNA
H33C H33C
=
DNA sequence
Accessible
DNA
Methylation
Histone
Wikimedia Commons
Combinations of Epigenetic Marks
Chemical Protein
e.g., Methylation e.g., Histones
DNA
Methyl
Histone
Nucleosome
Transcription
machinery
mRNA Histones
Modified from J. Corum for NYTimes
What do epigenetic marks do?
If DNA is like the alphabet, If DNA is like a book,
epigenetic marks are like the epigenetic marks are like
accents and punctuation sticky notes
DNA sequence
TAG CAT ACT
Re
a d
Ign
or
e
Epigenetic marks
Epigenetic marks tell our cells
whether and how to read the genes
What is Epigenetics? (Formal Definition)
• Epigenetics is the study of inherited traits caused by
mechanisms other than changes in the underlying DNA
sequence.
• Epi- = “above” or “upon”
• Framework for answering:
― How can the same DNA sequence lead to
different outcomes?
Wikimedia, NIDCD
How Does Epigenetics Affect Us?
Tissues have different epigenetic states
Diet and environment impact
your epigenetic state
Sisters? Actually, genetically identical.
Mothers were on different diets!
NIEHS, Wikimedia, flickr: anirudhkoul
Sources of Epigenetic Variation
Nature vs. Nurture
• Nature: Epigenetic marks can be inherited.
• Nurture: Epigenetic marks can be accumulated.
- Only those in germ line will be passed down.
Nature Nurture
Wikimedia Commons
Human (Epi)Genome Project
• Human Genome Project (1990-2003)
― Sequenced all ~20,000 genes in our DNA
― 3 billion basepairs, ~3 billion dollars
―Only 1.5% of genome codes for proteins!
• Epigenomics Road Map (2008-Present)
―Goal: Create map of epigenome in
multiple tissue types and cancers
Wikimedia Commons, NIH Roadmap Epigenomics
Summary
• Epigenetics is the study of heritable changes in gene
activity that do not involve alterations to the genetic code
• Epigenetic marks tell your genes to switch on or off
• Two types of marks: chemical (e.g., methylation) or
protein (e.g., histones)
• Through epigenetic marks, environmental factors like
diet, stress and prenatal nutrition can make an imprint on
genes passed from one generation to the next.
• Epigenetic changes can be inherited or accumulated
• Tissues have specific patterns of epigenetic modification
Thank you!
Questions?
