Basics of Epigenetics

1. CANCER
Towards a deep understanding
Hussein Sabit
Prof. of Cancer Epigenetics
College of Biotechnology, Misr University for science & Technology

4. Epigenetically ..
Identical twins are not
identical!

5. Epigenetics
Yes! the Ghost is ..

7.  Epi = above
 The studying of DNA changes, not involving
changes in sequence, that regulate gene
expression.
 It is s non-sequence-dependent inheritance.
ConradWaddington
Epigenetics

8. How nurture shapes
nature?

11. Despite that they were
originated from one single cell

12. Waddington Landscape

13. 1st trimester
2nd trimester
3rd trimester

14. 1. Genetic information :edivorpehtgnidliubkcolbrof
ehterutcafunamfolla proteins needed for the cell
activity.
2. Epigenetic information: provide additional
instruction on how, when and where these
information should be used.
2 Forms of information in a cell

15. Epigenetic information: provide additional instruction
on how, when and where these information should be
used.
Forms of information in a cell
AGAIN

16. Genetic alterations
Irreversible
Epigenetic alterations
Dynamic

17. 3 levels ..

18.  Epigenetic factors cause the
organism's genes to behave
differently.
 Normal to malignant transformation
 Cell differentiation
 Examples include:

19. Epigenetic Code Components

20. On Histone level
4. Ubiquitination
1. Acetylation
2. Methylation
3. Phosphorylation

22. Histone Modification
Most histone modification
occurs on the protrusions of
histone proteins.
Modification of Histone Tails

23.  Histones have a high percentage of basic amino
acids, which gives them an overall positive
charge.
 Positively charged amino acids associate with
the overall negative charge of the DNA.
Histone Modification

24. Histone Acetylation
Two enzymes involved in histone acetylation
 HAT
 HDAC
 The acetylation process eliminates the positive
charge from the amino acid.
 ⬆ acetylation = ⬆gene expression.

25. No expression Protein
mRNA

26. On the DNA level
• Cytosine methylation
This methyl cytosine mutations cannot be
identified and repaired.

28. Tissue Specific-methylation
E-Cadherin in Liver E-Cadherin in Skin=

29. E-Cadherin in Liver E-Cadherin in Skin
Tissue Specific-methylation
=

30. Tissue Specific-methylation
E-Cadherin in Liver E-Cadherin in Skin
≠=
Inactivegene
Activegene

31. Silencing is more important!
Creation of a neuron cell requires
silencing of about 35% of the cellular
genome.

32. Aging, methylation and
cancer

35. Identical twins with different hair greying level
Mosaicism:
An individual with two
different eye colors
Mosaicism:
An individual eye
with two colors

36. Is our experience heritable?

37. Lamarkism again!
 Inheritance of acquired
characteristics.
 Recent work in epigenetics
suggest that Larmark may have
been correct to some degree.
Transgenerational
soma-soma effects

38. Is our Epigenome
fragile?

39. Exposure to IR can induce genome instability in the
germline, and is further associated with transgenerational
genomic instability in the offspring of exposed individual.

40. High nourishment
Low nourishment
Queen-destined larvae
Worker-destined larvae
Queen-specific gene
expression and splicing
Worker-specific gene
expression and splicing
Genome
Totipotent
egg cell
Totipotent
1st instar
larvae
Normal expression and splicing of
house-keeping genes
• Queen
mandibular
pheromones
• Long life-span
(2yrs)
• Spermatheca
and active
ovaries
short life-span (2-
6 weeks)

41. Our Epigeneome could
be even affected by
Breathing in Diesel
Exhaust

42. What can SMOOTHLY affect your
epigenome?

43. What can SMOOTHLY affect your
epigenome?

44. What can SMOOTHLY affect your
epigenome?

45. VMAT2 gene

46. Methylation has impact on ..

47. The development of Depression

48. How People Respond to Fear and
Anger

49. Schizophrenia

50. Brain Feminization

51. Epigenetic drugs
o Cyclophosphamide
o Temozolomide
o Carboplatin
o Vorinostat
o Procaine
o Erlotinib
o 5-Aza
o etc.

59. Genomic Imprinting

60.  Parental of origin gene expression.
 For example: Insulin-like growth factor
2 (IGF2/Igf2) is only expressed from the allele
inherited from the father; this is called maternal
imprinting.
Genomic Imprinting

61. Regardless of whether they came from mom or dad,
certain genes are always silenced in the egg, and others
are always silenced in the sperm.

64. Epigenetic
reprogramming
Methylation/Demethylation
Cascade

65. Donkey
HorseHinny
Mule
Donkey
Donkey
Horse
Horse
Parent-of-origin effect is discovered
~3000 years ago in Asia.

66. Imprinting and Diseases
 Approximately 80 imprinted genes in the
human genome.
 Best characterised syndromes:
 Prader-Willi syndromes
 Angelman syndromes

67. Prader-Willi Syndrome
 One in 20,000 live births.
 Mostly sporadic due to paternal chromosome
deletion of 15 q11-q13.
Features include:
• Obesity, short, small hands/feet,
unusual facial features, mild mental
retardation.
• Hypogonadism.

68.  One in 25,000 live births
 Mostly sporadic
 Caused by deletion of the maternal
15q11-q13
Angelman Syndrome
• Speech impairment
• Easily excitable
personality
• Hypermotoric behavior
• Short attention span
Symptoms include:

69. Gene imprint also affect behavior!
Schizophrenia
A maternally imprinted gene (LRRTM1) shows
high expression during development throughout
the cortical plate.

70. Is it in our behavior also?

71. Bravery gene
 Official Symbol: KCNJ2
 Official Full Name: potassium channel, inwardly
rectifying subfamily J, member 2
 Gene type: protein coding
 Location: 17q24.3
 Exon count: 3

72. Lying gene
 Official Symbol: STK19 (G11)
 Official Full Name: serine/threonine
kinase 19
 Gene type: protein coding
 Location: 6p21.3
 Exon count: 9

73. Cheating gene
 Official Symbol: DRD4
 Official Full Name: dopamine receptor D4
 Gene type: protein coding
 Location: 11p15.5
 Exon count: 4

74. Suicide gene
 Official Symbol: TPH1
 Official Full Name: tryptophan hydroxylase 1
 Gene type: protein coding
 Location: 11p15.3-p14
 Exon count: 10

75. Criminal gene
 Official Symbol: MAOA
 Official Full Name: monoamine oxidase
 Location: Xp11.3
 Exon count: 16
 Gene type: protein coding

76. Depression gene
 Official Symbol: SLC6A4
 Official Full Name: solute carrier family 6
(neurotransmitter transporter),member 4
 Gene type: protein coding
 Location: 17q11.2
 Exon count: 15

77. You are ..
What your Mom ate & what your Dad did

78. Conclusion

79. Finally!

80. DNA is
NOT our
Destiny