1. L’ ‘epigenetica’ si riferisce a tutti i cambiamenti dell’espressione genica e dell’organizzazione della cromatina che sono indipendenti dalla sequenza del DNA.

2. -DNA methylation (5-mC, 5-hmC) -Histone PTMs (>100)
Epigenome provides instructions
and regulates the functional aspects of
all the genes
-DNA methylation (5-mC, 5-hmC)
-Histone PTMs (>100)

3. Monozygous twins share a
common genotype and are
genetically identical
There is significant
phenotypic discordance:
Mental disorders
Cancer

5. Age Dependent Epigenetic differences in Monozygotic (MZ) twins

6. Influence of Age on the Epigenome
in 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.

10. Figure 1 Associated potency in development and reprogramming for cell lineage (a) and social insect caste (b) specialisation. In both graphs, text in black boxes indicate the developmental stage in which lineage commitment occurs and text in grey boxe...
Solenn Patalano , Timothy A Hore , Wolf Reik , Seirian Sumner
Shifting behaviour: epigenetic reprogramming in eusocial insects
Current Opinion in Cell Biology, Volume 24, Issue 3, 2012,

11. Figure 2 A Waddington landscape for ant caste determination
Figure 2 A Waddington landscape for ant caste determination. Waddington's epigenetic landscape can be used as a metaphor for social insect caste determination.
Alexandra Chittka , Yannick Wurm , Lars Chittka
Epigenetics: The Making of Ant Castes
Current Biology, Volume 22, Issue 19, 2012, R835 - R838

12. Fig. 1 A summary of experimental evidence for induction of the queen phenotype in the honeybee as a result of diet signaling through TOR and IGF1/insulin nutrient sensing pathways to affect DNA methylation.
Dianne Ford
Honeybees and cell lines as models of DNA methylation and aging in response to diet
Experimental Gerontology, Volume 48, Issue 7, 2013,

13. Wolff et al. showed that providing excess folic acid, vitamin B-12, choline, and betaine to female mice before and during pregnancy shifts the coat color of their Avy/a offspring toward the brown (pseudoagouti) phenotype.
Waterland and Jirtle later demonstrated that this nutritionally induced change in phenotype occurs by increasing methylation at the Avy locus. Hence, the establishment of CpG methylation at Avy is sensitive to a dietary supplementation regimen designed to increase the efficiency of HCY remethylation.

17. . Waterland R A J. Nutr. 2006;136:1706S-1710S
©2006 by American Society for Nutrition

18. . Waterland R A J. Nutr. 2006;136:1706S-1710S
©2006 by American Society for Nutrition

21. Global perturbations of histones PTMs in human cancers.
H3K20me3 Lymphoma Fraga et al. Nat Genet
mouse SCC
H3K16ac (MOF) Lymphoma Fraga et al. Nat Genet
Breast, Medulloblastoma Pfister ey al. Int J Cancer 2008.
H3K4me2 (MLL) Prostate Seligson et al. Nature
H3K18ac Prostate Seligson et al. Nature
H3K9me2 Prostate, Kidney Seligson et al. Am J Pathol
Ellinger et al. Prostate 2010.
H3K18ac Lung, Kidney Seligson et al. Am J Pathol
Ellinger et al. Prostate 2010.
H3K27me3 (Pg) Prostate Yu et al. Caner Res

22. Colon
SUZ12
Colon
Prostate
EZH2
Breast
Breast
Skin
Liver
Lymphoma
Liver
Myeloma
Endometrial
Bladder
Lung
Gastric

23. ASH2L: important for trymetilation of H3 K4
MEN1
MEN1
MEN1
Molecular regulation of H3K4 trimethylation by ASH2L,
a shared subunit of MLL complexes
Melissa M Steward1, Jung-Shin Lee1, Aisling O’Donovan2,Matt Wyatt1,
Bradley E Bernstein2 & Ali Shilatifard1,3
SEPTEMBER 2006 NATURE STRUCTURAL & MOLECULAR BIOLOGY

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

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