EPIGENETICS
What is Epigenetics?
• The study of environmental factors on gene expression in DNA.
• The molecule is called methylation controls when genes are turned
on.
• Methylation turns off genes. Acetylation turn genes on.
What is
Epigenetics?
Watch the video
History of Epigenetics
• Discovered by Paul Kammerer, a lamarckian evolutionist, in the 1920s.
• The midwife toad experiment was controversial and soon found to have been fraudulent.
• Recent review of his experiment has shown it to be possible.
Epigenetic Inheritance
• Genetic tags are passed down through generations
• When the zygote is formed many epigenetic tags are removed from the chromosomes of the parents, but some remain
Epigenetic Inheritance cont.
• Previously believed that genetic information was passed through DNA only
• Studies in the field of epigenetics shows that parent‟s experiences are passed on to offspring through epigenetic tags
Identical Twins
• Identical twins are from the same zygote, so they begin life with the same genetic information, including epigenetic tags
• While infants they experience the same or very similar environments, so there is little variation in the epigenome
• Over time the twins‟ environments will diverge, resulting in individual epigenetic tags to form for each twin
Identical Twins cont.
• The difference in the twins‟ epigenomes is what makes them become different when they are older
• The epigenetic tags can have such an effect on the twins that one can develop a disease while the other is fine
• When this situation occurs, researchers will try to pinpoint the environmental factors that are responsible for the disease
Environmental Factors
• The major factors that affect the epigenome are:• Stress
• Social interactions
• Physical activity
• Exposure to toxins
• Diet
• No specified yet
• The nutrition of the mother can affect the epigenome of a fetus
• Stress hormones also travel from the mother to a fetus to affect the epigenome
•
Monozygous twins share a common genotype and aregenetically identical
There is significant phenotypic discordance:Mental disordersCancer
Agouti “Twin” Sisters
Coat Colors of Genetically Identical Agouti
Mice Liter Mates
Coat color serves as a sensor for the degree of methylation present
Mosaicism:
An Individual with Two Different Eye Colors
“Diego”
Mosaicism:
An Individual Eye with Two Colors
Bisphenol A
Epigenetics
• C.H. Waddington coined the term epigenetics to mean above or in addition to genetics to explain differentiation.
• How do different adult stem cells know their fate?• Myoblasts can only form muscle cells
• Keratinocytes only form skin cells
• Hematopoetic cells only become blood cells
• But all have identical DNA sequences.
• Modern definition is non-sequence dependent inheritance.• How can identical twins have different natural hair colors?
• How can a single individual have two different eye colors?
• How can identical twin liter mates show different coat colors?
• How can just paternal or maternal traits be expressed in offspring? This is called genetic imprinting.
• How can females express only one X chromosome per cell?
• How can acquired traits be passed on to offspring?
• Some changes in gene expression that are, in fact, heritable!
What is Epigenetics?
• Epigenetics refers to the study of changes in the regulation of gene
activity and expression that are not dependent on gene DNA
sequence
• Epigenetics is the study of environmental factors on gene expression
in DNA.
• Methylation turns off genes.
• Acetylation turn genes on.
• While epigenetics often refers to the study of single genes or sets of
genes, epigenomics refers to more global analyses of epigenetic
changes across the entire genome.
Three Levels of Folding of DNA in
Chromatin
Methylated DNA from Zygote to Adult
DNA Methylation Differentiates Totipotent Embryonic Stem Cells
from UnipotentAdult Stem Cells
DNA Methylation Differentiates Totipotent Embryonic Stem Cells
from UnipotentAdult Stem Cells
DNA Methylation Differentiates Totipotent Embryonic Stem Cells
from UnipotentAdult Stem Cells
Differentiated Cells can
Become Totipotent
Critical CpG Sequences in
CpG Islands Near Promoters
Organization of the Epigenome
Epigenetic Imprinting
Methylation Changes During Development
Epigenetics Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
The term
„epigenetic‟
It refers to all
heritable changes in
gene expression and
chromatin
organization that are
independent of the
DNA sequence itself.
• Transcriptionally active chromatin regions tend to be hyperacetylated and hypomethylated.
• If a region of DNA or a gene is destined for silencing, chromatin remodeling enzymes such as histone deacetylases and ATP-dependent chromatin remodelers likely begin the gene silencing process.
• One or more of these activities may recruit DNA methyltransferase resulting in DNA methylation, followed finally by recruitment of the methyl-CpG binding proteins.
• The region of DNA will then be heritably maintained in an inactive state.
Methylation of Cytosine in DNA
Paula Vertino, Henry Stewart Talks
5-Methyl Cytosine in DNA
Paula Vertino, Henry Stewart Talks
DNA Methylation
Hypomethylation
Hypermethylation
DNA Methylation and Cancer
RNA Interference (RNAi)
Summary of Epigenetic Gene Regulation
• Patterns of DNA methylation in adult cells parallels cell
fate, chromatin structure and gene activation.
• Most DNA methylation is removed at fertilization and re-
established during embryogenesis.
• Imprinted genes keep their parental pattern of methylation
giving rise to parental patterns of expression.
• Patterns of histone modifications parallel DNA
methylation.
Summary of Epigenetic Gene Regulation
• Methylated gene regions are genetically inactive, highly condensed and special histone modifications.
• Active gene regions have little DNA methylation and distinctive histone modifications (acetyl groups and H3K4methyl).
• X chromosome inactivation in females is correlated with extensive CG island methylation on one chromosome, condensation, inactivation and Barr body formation.
• Alterations in gene and CG island methylation patterns are seen in aging and in cancer.
• Most CG islands are not methylated except for X chromosome inactivation and tumor suppressors in cancer.
Epigenetics in Medicine
• Epigenetics can help us
master stem cells.
• With that knowledge we
may be able to control
changing stem cells.
• Epigenetics has opened a
new field in genetic
research.
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