1. Epigenetics
• ‘Epi’genetics - ‘On’ or ‘over’ the genetic
information encoded in the DNA

2. Epigenetics
• The study of reversible heritable changes
in gene function that occur without a
change in the sequence of nuclear DNA
• Gene-regulatory information that is not
expressed in DNA sequences is
transmitted from one generation (of cells
or organisms) to the next

3. Epigenetics and
Different Aspects of Life
• Development of multicellular organism
• Environment-organism interaction
For examples: Nutrition supplements and environmental toxins
Image: Randy Jirtle
• Pathogenesis of diseases

4. Molecular Mechanisms that
Mediate Epigenetic Phenomena
• DNA methylation (CpG dinucleotides)
• Histone modifications
Nucleosome

5. Histone Modifications
Adapted from Lund and Lohuizen Genes Dev 2004

6. Epigenetic Regulation of Gene Expression
• Epigenetic information modulates gene
expression without modifying actual DNA
sequence
• Histone modifications change the
chromatin structure and affect the
accessibility of DNA to regulatory proteins

7. Epigenetic Regulation of Gene Expression
Methylated
DNA
Histone

8. Histone Modification Status Correlates with
Transcriptional Activity
• Gene activation correlated with H3-K9 acetylation
• Gene silencing associated with H3-K9 methylation

9. Epigenetic Inheritance
• Transmission of non-DNA sequence information
through either meiosis or mitosis
• When a methylated DNA sequence replicates,
only one strand of the next-generation double
helix has all its methyl markers intact; the other
strand needs to be remethylated
• Maintenance methylase theory
– DNA methyltransferases (DNMTs): Enzymes that bind
methyl groups to cytosine nucleotides
– DNMTs bind methyl groups to the naked cytosines
based on the methylation template provided by the
other strand-

10. Epigenetics and Cancer
• Chromosomal infrastructure is essential for gene control,
determining both active and repressed states
• It is important not only to turn the right genes on but also
to turn the right genes off
• Histones and chromatin components have key roles in
this decision making process
• If as few as three inappropriate genes are turned off, a
normal cell can be converted into a cancer cell
• This epigenetic silencing of genes underlies a new
approach to cancer therapy
• Mistargeting of these enzymes leads to tumorigenesis,
but inhibition of their activity presents a novel approach
to therapy