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EPIGENETICS

SANJEEVKUMARPALB 6252Jr.MSc.DEPARTMENT OF GENETICS AND PLANT BREEDING.

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EPIGENETICS

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QUESTIONS ????? 1.HOW EMBRYONIC STEM CELLS DIFERENTIATE INTO NERVE CELL,BRAIN CELL ,HEART CELL etc. WITH DIFFERENT FUNCTIONS,EVEN THOUGH ALL CELLS CONTAIN SAME DNA ?

2.WHY ONE IDENTICAL TWIN SUFFER FROM DISEASE(CANCER) AND OTHER DOESN’T ?

3.WHETHER OUR LIFE STYLE CAN INFLUENCE OUR CHILDREN AND GRANDCHILDREN GENOTYPE….?

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CONT…4. WHETHER WE CAN CONTROL OUR DNA.?

5.WHY DO PLANTS BLOOM IN ATUMN BUT NOT IN WINTER.

6.WHETHER LAMARK WAS 100% WRONG ???

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Epigenetics • The term EPIGENETICS coined by

- Waddington in 1942.

• Epigenetics literally means “above”Or “ on top of” genetics.• All genetic modification s excluding change in DNA.“CHANGE IN PHENOTYPE WITHOUT CHANGE IN

GENOTYPE.”

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A. TATACATGCACC

B. TATACTTGCACC

C. TATACATGCACC

Phenotype

Phenotype

Phenotype

m m

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Epialleles are alleles of a locus which have identical DNA sequences but display different epigenetic states, and which have been proposed to influence a variety of phenotypes in plants and animals (Richards 2006).Epigenomics- Global analyses of epigenetic changes across the entire genome.

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1.How embryonic cell differentiate ?

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Brain Heart Nerve

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Brain Heart Nerve

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Nerve

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(Tumour repressor gene in cancer. )

2.Why one identical twin suffer from disease and other one doesn't ?

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MECHANISMS • DNA methylation

• Histone modifications Acetylation Methylation Phosphorylation,Ubiquitination• RNA mediated

interference

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The resulting 5-methyl cytosine (5mC) is often repressive and can lead to gene silencing (Cedar and Bergman 2012). The repressive nature of 5mC is thought to inhibit the binding of DNA by transcription factors (Watt and Molloy 1988) or to recruit additional chromatin proteins to form heterochromatic state that is inaccessible for transcription.

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Cytosine methylation in plants occur in the contexts of :

CG CHGCHH (H=A, C or T)

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MAINTENANCE METHYLATION

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HISTONE MODIFICATIONS

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Histone Acetylation & Deacetylation Histone acetylation

– Histone acetyl transferases (HATs) Adds acetyl groups to histone tails Reduces positive charge and weakens interaction of histones

with DNA Facilitates transcription by making DNA more accessible to RNA

polymerase II Histone deacetylation – Histone deacetylases (HDACs) Removes acetyl groups from histone tails Increases interaction of

DNA and histones Represses transcription

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Effects of Acetylation• -ve charge on histone

• reduces affinity of tail for adjacent nucleosomes

• creating a transcription permissive environment

• increase the access of transcription factors

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Histone Methylation Histone methylation • Histone methyl transferases (HMTs) – Histone lysine methyl transferases(HKMTs)

Methylate lys (k) residues • Protein argenin methyl transferase (PRMTs) Methylate arge(R) residues• Methylation can result in activation or repression of expression Trimethylation of histone H3 at lysine 4 (H3K4) is an active mark

for transcription Dimethylation of histone H3 at lysine 9 (H3K9), a signal for

transcriptional silencing

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Effects of Histone methylation

• Methylation does not neutralize charge but recruit silencing

or regulatory proteins that bind methylated histones.

• transcription repression

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Fig. Different modifications of histones lead to different states of chromatin architecture,which affects gene expression.

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PHOSPHORILATION

•Phosphorylation increase the negetive charge on Heston as a result less interaction betwen DNA and Histones. chromatin decondensation.

•Dephosphorylation increase positive charge followed by chromatin condensation.

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RNA MEDIATED SILENCING

• Involvement of sRNAsMicro RNAsSmall interfering RNAs

• RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression , typically by causing the destruction of specific mRNA  molecules.

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EXPERIMENTS WITH EPIGENETICS

• HOW OUR LIFE STYLE CAN INFLUENCE ON OUR PROGENY?- Men who smoke before puberty tend to have sons

who can’t produce sperm, have higher body mass indexes and shorter life expectancies.

- Smoking and over-eating can make the genes for obesity over-express themselves and the genes for longevity under-express themselves.

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YOU ARE WHAT YOUR GRANDMOTHER ATE.

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WHETHER EPIGENETIC MARKS ARE INHERITED ?

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WHETHER WE CAN CONTROLE OUR DNA ?

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GOOD NEWS• Scientists are learning to manipulate epigenetic

marks and are making drugs that will treat sickness by turning off the bad genes and turning on the good ones. • Scientists are hoping to develop epigenetic drugs to

help people with diabetes, cancer, Alzheimer’s, schizophrenia, autism, etc.

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IMPLICATIONS IN AGRICULTURE.Vernalization and epigenetics:

how plants remember winter

One of the remarkable aspects of the promotion of flowering by vernalization is that plants have evolved the ability to measure a complete winter season of cold and to ‘remember’ this prior cold exposure in the spring.

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Transgene Silencing• Transgenes do not express as expected• Expression of transgenes are suppressed in

transgenic plants after they have grown for one or more generation is called gene silencing• Because • Stress induced transgene inactivation-

transgene that are integrated into genomic regions which are subjected to epigenetic modifications during stress treatment are succeptible to environmentally indced silensing

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Plant stress tolerance: – Methylation pattern changes during stress helps

plants to tolerate stressGenomic Imprinting:- Parental genome equilibrium required for proper

seed development (2:1 maternal to paternal genome for proper endosperm development

Epigenetic VariationSoma clonal variation

OTHER IMPLIICATIONS

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Contributions to Science Work and Society• The new evidence for epigenetic inheritance has

had great implications for the study of evolution.

• It extends the span of evolutionary thinking and is leading to ideas of heredity that include development.

And it also suggests that acquired traits can be

heritable, so Lamarck wasn’t completely wrong

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THANK YOU