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What Is Epigenetics ?What Is Epigenetics ? What Is Epigenetics ?What Is Epigenetics ?

Shirish Barve Professor

Department of Internal MedicineDivision of Gastroenterology/Hepatology

The term ‘epigenetic’ refers to all heritable changes in gene expression and chromatin organization that are independent of the DNA sequence itself.

Epigenome provides instructions and regulates the functional aspects of

all the genes

Scientists Find Clue To Mechanisms Of Gene Signaling And Regulation (Aug. 23, 2007)

Epigenetics To Shape Stem Cell Future (Feb. 23, 2007)

Human Embryonic Stem Cells Remain Embryonic Because Of Epigenetic Factors (Oct. 8, 2007)

Epigenetic Changes Discovered In Major Psychosis (Mar. 12, 2008)

Epigenetics May Be The Underlying Cause For Male Infertility (Dec. 13, 2007)

Monozygous twins share a common genotype and aregenetically identical

There is significant phenotypic discordance:Mental disordersCancer

Transcriptionally active chromatin regions tend to be hyperacetylated andhypomethylated. 

If a region of DNA or a gene is destinedfor silencing, chromatin remodeling enzymes such as histone deacetylasesand ATP-dependent chromatin remodelers likely begin the gene silencing process. 

One or more of these activities mayrecruit DNA methyltransferase resulting in DNA methylation, followed finally by recruitment of themethyl-CpG binding proteins.

The region of DNA will thenbe heritably maintained in an inactive state.

Age Dependent Epigenetic differences in Monozygotic (MZ) twins

In the early years of life the younger MZ twins are epigenetically indistinguishable

Older MZ twins exhibit remarkable differences in their epigenome as evidenced by changes in the:overall content and genomic distribution of 5-methylcytosine DNA and

histone acetylation, affecting their gene-expression portrait.

Influence of Age on the Epigenome in MZ Twins

Epigenetics stands at the center of modern medicine because epigenetic changes, unlike DNA sequence which is the same in every cell, can occur as a result of dietary and other environmental exposure

Environment &Epigenome

Mounting evidence suggests that fetuses are surprisingly susceptible to outside influences such as environmental pollutants, pesticides, and other toxins.

Agouti “Twin” Sisters

Coat color serves as a sensor for the degree of methylation present

Bisphenol A

Bisphenol A

Bisphenol A

Bisphenol A

Bisphenol A

With minor exceptions, all differentiation processes are triggered and maintained through epigenetic mechanisms.

Epigenetic inheritance is an essential mechanism that allows the stable propagation of gene activity states from one generation of cells to the next.

DNA Is Not Destiny The new science of epigenetics rewritesthe rules of disease, heredity, and identity.