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
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
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