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EPIGENETICS
SANJEEVKUMAR
PALB 6252
Jr.MSc.
DEPARTMENT OF GENETICS AND PLANT
BREEDING.
13-01-2017
•
213-01-2017
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….?
313-01-2017
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 ???
413-01-2017
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.”
513-01-2017
613-01-2017
A. TATACATGCACC
B. TATACTTGCACC
C. TATACATGCACC
7
Phenotype
Phenotype
Phenotype
m m
13-01-2017
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
9
1.How embryonic cell
differentiate ?
13-01-2017
1013-01-2017
1113-01-2017
Brain Heart Nerve
1213-01-2017
Brain Heart Nerve
1313-01-2017
Nerve
1413-01-2017
15
(Tumour repressor gene in
cancer. )
2.Why one identical twin suffer from disease and other one doesn't ?
13-01-2017
MECHANISMS
13-01-2017 16
• DNA methylation
• Histone modifications
Acetylation
 Methylation
 Phosphorylation,
Ubiquitination
• RNA mediated
interference
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.
13-01-2017
Cytosine methylation in plants occur in the
contexts of :
 CG
 CHG
CHH (H=A, C or T)
1813-01-2017
MAINTENANCE METHYLATION
1913-01-2017
HISTONE MODIFICATIONS
2013-01-2017
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
13-01-2017 21
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
13-01-2017 22
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
13-01-2017 23
2413-01-2017
Effects of Histone methylation
• Methylation does not neutralize charge but recruit silencing
or regulatory proteins that bind methylated histones.
• transcription repression
13-01-2017 25
26
Fig. Different modifications of histones lead to different states of chromatin architecture,
which affects gene expression.13-01-2017
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
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
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.
2913-01-2017
3013-01-2017
YOU ARE WHAT YOUR GRANDMOTHER ATE.
13-01-2017 31
WHETHER EPIGENETIC MARKS
ARE INHERITED ?
3213-01-2017
WHETHER WE CAN CONTROLE OUR DNA ?
3313-01-2017
3413-01-2017
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
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.
3613-01-2017
3713-01-2017
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
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
13-01-2017
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
4113-01-2017
4213-01-2017

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Epigenetics: How embryonic stem cells differentiate and identical twins can have different diseases

  • 1. 1 EPIGENETICS SANJEEVKUMAR PALB 6252 Jr.MSc. DEPARTMENT OF GENETICS AND PLANT BREEDING. 13-01-2017
  • 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….? 313-01-2017
  • 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 ??? 413-01-2017
  • 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.” 513-01-2017
  • 7. A. TATACATGCACC B. TATACTTGCACC C. TATACATGCACC 7 Phenotype Phenotype Phenotype m m 13-01-2017
  • 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
  • 15. 15 (Tumour repressor gene in cancer. ) 2.Why one identical twin suffer from disease and other one doesn't ? 13-01-2017
  • 16. MECHANISMS 13-01-2017 16 • DNA methylation • Histone modifications Acetylation  Methylation  Phosphorylation, Ubiquitination • RNA mediated interference
  • 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. 13-01-2017
  • 18. Cytosine methylation in plants occur in the contexts of :  CG  CHG CHH (H=A, C or T) 1813-01-2017
  • 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 13-01-2017 21
  • 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 13-01-2017 22
  • 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 13-01-2017 23
  • 25. Effects of Histone methylation • Methylation does not neutralize charge but recruit silencing or regulatory proteins that bind methylated histones. • transcription repression 13-01-2017 25
  • 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. 2913-01-2017
  • 31. YOU ARE WHAT YOUR GRANDMOTHER ATE. 13-01-2017 31
  • 32. WHETHER EPIGENETIC MARKS ARE INHERITED ? 3213-01-2017
  • 33. WHETHER WE CAN CONTROLE OUR DNA ? 3313-01-2017
  • 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. 3613-01-2017
  • 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 13-01-2017
  • 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

Notas do Editor

  1. JAN 18 2010 .TIME.
  2. 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
  3. Maintainance of CHH and GHH BY De novo RNA directed methylation.
  4. 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.
  5. 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
  6. Mecp 2 proteine and Hp1 proteine.
  7. 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).
  8. 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.
  9. 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