epigenetics - an-najah national university

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.