11. H2B: 14 modified Lysines (mass-spec)
PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQVH
PDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLL
LPGELAKHAVSEGTKAVTKYTSSK
5 11 12 15 16 20 23 24 27 30 34 43 46
57 85
108 116 120 125
a1
a2 a3
aC
L1 L2
LC
Ac AcAc AcAc Ac Ac
Ac
Ac
Me Me Me
Me
Ub
Ac
Ac
Ac
12. H2B: abs against modified Lysines
PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQVH
PDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLL
LPGELAKHAVSEGTKAVTKYTSSK
5 11 12 15 16 20 23 24 27 30 34 43 46
57 85
108 116 120 125
a1
a2 a3
aC
L1 L2
LC
Ac AcAc AcAc Ac Ac
Ac
Ac
Me Me Me
Me
Ub
Ac
Ac
Ac
Me Me
Ac
13.
14. Transcriptionally active chromatin
regions tend to be hyperacetylated and
hypomethylated.
If a region of DNA or a gene is destined
for silencing, chromatin remodeling
enzymes such as histone deacetylases
and ATP-dependent chromatin
remodelers likely begin the gene
silencing process.
One or more of these activities may
recruit DNA methyltransferase
resulting in DNA methylation,
followed finally by recruitment of the
methyl-CpG binding proteins.
The region of DNA will then
be heritably maintained in an
inactive state.
17. 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.
Influence of Age on the Epigenome
in MZ Twins
18. The epigenome of our cells
changes following changes
in the environment and diet.
The genome is the same in
every cell (bar few
exceptions).
19.
20. Environment & Epigenome
Mounting evidence
suggests that
fetuses are
surprisingly
susceptible to
outside influences
such as
environmental
pollutants,
pesticides, and other
toxins.
24. 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.
32. ASH2L: important for trymetilation of H3 K4
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
MEN1
MEN1
MEN1
33.
34. With minor exceptions, all differentiation
processes are triggered and maintained
through epigenetic mechanisms.
35. Epigenetic inheritance is an essential
mechanism that allows the stable
propagation of gene activity states from
one generation of cells to the next.
36. DNA Is Not Destiny
The science of
epigenetics rewrites
the rules of disease,
heredity and identity.
