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

Epigenetics

-DNA methylation (5-mC, 5-hmC) -Histone PTMs (>100)

3 Years old

50 Years old

Age Dependent Epigenetic differences in Monozygotic (MZ) twins

Comparison of 5mC DNA Content and Histone H3 and H4 Acetylation Levels in MZ Twin Pairs.

PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQV

HPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRL

LLPGELAKHAVSEGTKAVTKYTSSK

5 11 12 15 16 20 23 24 27 30 34 43 46

57 85

108 116 120 125

1

2 3

C

L1 L2

LC

H2B: 19 Lysines

H2B: 14 modified Lysines (mass-spec)

PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQV

HPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRL

LLPGELAKHAVSEGTKAVTKYTSSK

5 11 12 15 16 20 23 24 27 30 34 43 46

57 85

108 116 120 125

1

2 3

C

L1 L2

LC

Ac AcAc AcAc Ac Ac

Ac

Ac

Me Me Me

Me

Ub

Ac

AcAc

H2B: abs against modified Lysines

PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQV

HPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRL

LLPGELAKHAVSEGTKAVTKYTSSK

5 11 12 15 16 20 23 24 27 30 34 43 46

57 85

108 116 120 125

1

2 3

C

L1 L2

LC

Ac AcAc AcAc Ac Ac

Ac

Ac

Me Me Me

Me

Ub

Ac

AcAc

Me MeAc

H2B: abs against K46ac, K46me2

PEPAKSAPAPKKGSKKAVTKAQKKDGKERKRSRKESYSIYVYKVLKQV

HPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRL

LLPGELAKHAVSEGTKAVTKYTSSK

5 11 12 15 16 20 23 24 27 30 34 43 46

57 85

108 116 120 125

1

2 3

C

L1 L2

LC

Ac AcAc AcAc Ac Ac

Ac

Ac

Me Me Me

Me

Ub

Ac

AcAc

AcMe

???

Histone methylation