3. 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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4. 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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5. 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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8. 8
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.
13-01-2017
17. 17
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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18. Cytosine methylation in plants occur in the
contexts of :
CG
CHG
CHH (H=A, C or T)
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21. 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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22. 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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23. 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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25. 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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26. 26
Fig. Different modifications of histones lead to different states of chromatin architecture,
which affects gene expression.13-01-2017
27. PHOSPHORILATION
27
•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.13-01-2017
28. RNA MEDIATED SILENCING
• Involvement of sRNAs
Micro RNAs
Small interfering RNAs
28
• RNA interference (RNAi)
is a biological process in
which RNA molecules inhibit
gene expression , typically by
causing the destruction of
specific mRNA molecules.
13-01-2017
29. 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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35. 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.
3513-01-2017
36. 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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38. 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
3813-01-2017
39. Plant stress tolerance: –
Methylation pattern changes during stress helps
plants to tolerate stress
Genomic Imprinting:-
Parental genome equilibrium required for proper
seed development (2:1 maternal to paternal
genome for proper endosperm development
Epigenetic Variation
Soma clonal variation 39
OTHER IMPLIICATIONS
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40. 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
4013-01-2017
The epigenotype refers to mitotically heritable patterns of DNA methylation at CpG dinucleotides and modifications to chromatin proteins (e.g. histone acetylation) that package DNA.
Pure epialleles -which is solely epigenetic, meaning that they are independent of the genetic variations.
2. which are not fully dependent on genetic variation, meaning they could be partly attributableto both genetic and epigenetic differences
3. which are directly determined by genetic variants and co- segregate with these methylation variants
Maintainance of CHH and GHH BY De novo RNA directed methylation.
Acetylation of histones is thought to relax condensed heterochromatin as the negative charge of acetyl groups can repel the DNA phosphate backbone charges, thus reducing the histone binding affinity for DNA.
Methylation of histone can occur on lysine (K) or arginine (R) residues leading to either transcriptional activation or repression.
Covalent addition of one, two, or three methyl groups (me1, me2, or me3) mainly occurs on H3K4, H3K9, H3K27, H3K36, and H4K20, andthis function is exerted through histone methyltransferases (HMTs).
R-only occurs in mono- and di-methyl states
Mecp 2 proteine and Hp1 proteine.
inactive chromatin (heterochromatin) is more methylated in both histones and DNA in comparison to active euchromatin, which is generally less methylated. This is particularly true for H3K9, H3K27, H3K79, and H4K20 methylations (Fig. 2.2).
Capped and polyadenylated transcripts of nuclear RNA Pol II that
form imperfect hairpins serve as the precursors for miRNAs. DCL1 cleaves these precursors with the help of the HYL1, DDL1, and SE nucleic acid–binding proteins. Diced products are end-methylated by HEN1 and exported to the cytosplasm in a process involving the exportin 5 homolog, HST. In association with AGO1 or a related AGO protein, such as AGO10, the miRNA guides the cleavage or translational inhibition of complementary mRNAs. Nuclear functions in which miRNAs are implicated include specific cases of cytosine methylation, trans-acting siRNA (tasiRNA) production or pre-mRNA degradation.AGO 1-ARGONAUT 1.DCL- DICER LIKEHEN .HEN -HUA ENHANCER.HYL 1-hyponastic leaves.DDL –DAWDLE.RISC RNA induced silencing complex.
A key component of the vernalization pathway, VERNALIZATION INSENSITIVE3 (VIN3), which is a PHD-domain-containing protein, is induced only after a prolonged period of cold. VIN3 is involved in initiating the modification of FLC chromatin structure.
Addresses Department of Biochemistry, University of Wisconsin–Madison, 433 Babcock Drive, Madison, Wisconsin 53706, USA 1e-mail: sbsung@biochem.wisc.edu 2e-mail: amasino@biochem.wisc.edu