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i n

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m

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l e

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r o

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n m

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i n g l s

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o

r o t e in a s d e n o m

o n t o s q u e s e p u e d e n d is t in g u i r a l m

so m

o r s u s s i la s e n
g

(p

co n

is

dc n

) ,

i a

in

r a s a

u ra

c o n s tit u id o

is i6 n

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r o

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)
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lo s 6 1 a

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Es tru c tu ra

, f u

c l6

l
La

in f o r m

qu

e v e r co n

n a s,

f lu

d c

r m

0 6

10

i n

t e

so b re e l D

c 6 d ig o s e p i g e n t i c o s
N A

u n a

d e

s e r ie

s e

r e

s e

a t in a t ie n e

t a d e la c r o m
p a c

r c la j a d a o c o m

a c i6 n

rm

ic a s q u e o c u r r e n t a n t o

as o

r ia l

a le

E P IG E N E T IC A

r m

t e

d e l D

m i l a c i 6 n

ll s ts

c o m
n

c o

i f ie s t a n

a n

t i n

c a m

i 6

io

lo s

e n

ic a s

o d if ic a c io n e s b io q u im

l a s h is t o

e n

in o s d e la s h is t o n a s

o s a m

e x t re m

e s t o s d o s s is t e m

e 1 e sta d o

e n

]a c o n b

o d ific a c io n e s q u im

i n

r e v is a r 5 n

se

q u c d e t e r m i n a

a c i6 n

M E T IL A C I6 N D E L D N A
A dem
qu
p

b a s e s ( g u a n in a

a s d e la s c u a t ro

estrs

al D N

d e d a rio

o x id a n t e

, y

t a n

c o

t o

la

s ic i 6

e n

a , t im

in

e s t a s

la

in

id

id

r o x

a s e s

s in

c it o

e s o

s e

) ,

x ig

a n

a s

if i c a d

in

e l

e n

fi g u r a

a n in a
s

e s t a d

lo

a l

e l e s ta d o

d e

l a

ia

s e

c 6 d ig o

p le jo

c o m

u n

e s

r a

r e n

ife

e l c o n t r a r io )

r e

a d

e n

g
a

o r

t r

c o n s id e r a n

s e

t a

l a

c o n t r ib u y e

q u e

f i e

t il a

a l

f o

r e

s f a

y
t o

t e

in

t il a d

f m

i o

t r e

s e

i t o

a d

l a

in

i a

"

ca m

s e c u e n c ia s

r ic o s e n

N A

e n

e t ila c i6 n

r e

s e

e n to s d e

e t il a c i 6

d e

"

"

c ie r t o s s e g m

"

e s tr a c 6 m

e sta d o s

d o s

'
C

E x is t e n

lo s

u e st r a

m
'

la g u
CpG

s e

t r a n s c r i p c io n a l

ie n t o

o s ile n c ia m

d e a c t iv id a d
6

a d a d u p la ) 5

X
8

(lla m

p a r te

c o m

re c o n o c e n

se

a s p o s ic io n e s y

re g u la r e l e st a d o

d e c it o s in a s e n p o s ic i6 n 5

e t il a c i6 n

la m

is m

s e

e n

r e in d iv id u o s O t r a s m o d ific a c io n e s ,
t e e n c a d a c l u l a y m u y v a r ia b le e n t
'
'
'
c o m

e ll a s s e

u c h a s d e

o d ific a d a s

d e b a se s m
c a s o

e l

a d

e ria s c a n t id a d e s d e u n a d iv e r s id a d

ro d u c to

e n

b ia

a n

la r g o

d e

Io

e s

C p G

s,

in

i c o

5 m

lla m

la

o n t o g e n ia

la

c ia d a s L a p r e s e n c i a d e l w
e s t n m 5 s d if e r e n
a y o r c o n fo r m e la s c l u l a s
m e t il t r a n s fe r a s a s , m i e n t r a s q
t iv id a d d e D N A
c it o s in a d e p e n d e d e l a a c
A
D
N
a s d e
e p e n d e d e l a s d e s m e t ila s

fi

i s l a

r a

t ie n d e

p o

e t il o

se r

e n

la

e li m

s u

in

a c i6

Y E U C R O M A T IN A

EL D N A Y H ET E R O
ESTA D O D E MET IL AC IO N D

0 0 0

la m

it a d

la s

r e g io n e s d e c o n t r o l e n

a y o r p a r te d e

"

"
s

i s l a

h e t e ro c r o m
c o n d e n sa d a q u e c o rre s p o n d e a
"
"

la s

i s la s

n a y c o r re s p o n d e n

it e s 5

c a re c e

a t in a y
s t a

t il a

a n

'

L o s lim

d e lo s g e n e s

d c m
u n a a lt a d e n s ila d
c e n s e r Ja s 5 r e a s r e le v a n t e s d o n d e

e l c o n t r a r io
a

la s c a s i 3 0

La

s o

i a

l a

d e

a c t i v id a d

i6

s e

in

is l a s

l a n

r o

r e

a t in a

t r a n s c r ip c io n a l
u

"

"

'
y

e t ila c io n e s s e lig a c o n c r o m

P o r
a t i

s o p r e s e n t a n u n a f r a n c a t ra n s c r i p c i6 n
d e n s e r t r a n s c r it o
a g e n es q u e p u e

a c t iv a

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C A P LT U L D

a s

o s o m

ro m

d e

n c l e o

se

e u c a n o ta s y

la s c l u l a s

S e e n c u e n t r a n e n e l in t e r io r d e l
t e ii ir s e c o n a ig u
d a d q u e t ie n e n d e
lla m a n c r o m o s o m a s , p o r la p r o p ie
som a
o lo r y
ia b r a e s d e o r ig e n g r ie g o : c h r m n o s c
n o s c o lo r a n t e s (la p a
e s
p e c ia l
o a p r o t e in a s , e n
E s t 5 n fo r m a d o s p o r D N A u n id
c u e r p o )
o
r u n a
o
s
t u id
p
m o s o m a s e s t 5 n c o n s ti
h is to n a s D e m a n e r a b 5 s ic a , lo s c r o
t r o , c o m p u e s to p o r
d e 1 1 0 d e d i5 m e
a m e n t o e le m e n t a l
-

a t r iz

lil

r e p e t id a s ,

u n id a d e s

molculas d e
de
U n

u n o s 2 0 0

lo

n u c l e o s o m a

a lr e d e d o r d e

h is t o n a s

(p b )

b a se s

d e
p a re s

se

e n r o lla

e n to

se g m

la s c u a le s u n

v u e lt a

u n a

"

molcula d e

(tin k e ?

i6 n

a s,

lo s n u c le o s o m

e s

'

c u a rto s
-

ingis) d e

o n ad o s
u e

e tro

d e

a d o s n u c le o

la b

o c h o

p o r

tre s

n e
e s p a c ia d o r e s e l q u e u
"

N A
u e fi o s e g m e n t o d e D
p eq
o n u n a
s o m a s y s e a s o c ia c
e le m e n t a l d e
t
o
e
n
h is to n a E l 6 1a m

c o n s t it u id o

u n o

cad a

su

e s v is ib l e

d e d i5 m
0
, q
r m a u n a fib r a d e 3 6
y fo
r
o
s c o p io e le c t r 6
l
m
ic
d
e
t
r
a
v
s
a
n lo s c r o m o s o m a s
c u a n d o s e e x a m in a
t in a
a L a s a s a s d e b r a s d e c r o m a
li b r a d e c r o m a t in
n ic o y c o n s t it u y e l a
as E n
e c h a d e p r o t e in a s n o h is t o n
e s t r u c tu r a c e n t r a l h
s e a d h ie r e n a u n a
a t o p o is o m e r a s a I I , q u e p u e d e m
lla m ie n t o , la p n p Im
e s te p u n t o d e e n r o
d e n a , p e rm it e q u e la s a s a s d e D N A
t u r a s d e d o b le c a
u c ir y r e p a r a r r u p
a n d a m ia e c e n t r a l L a s f ib r a s d e c r o
5 s a lr e d e d o r d e l
se c o m p a c te n m
n a d n m 5 s d u r a n t e la m e t a fa s e p a r a
d a m ia e s e e n r o lla
m a t in a e n e s t e a n
c o n
o ll a m ie n t o o r d p n a d o d e 1 D N A
m o so m a s E I e n r
c o n fo r m a r lo s c r o
m a n e r a a p r o x im a ia
t o n a s p e r m it e q u e d e
is t o n a s y n o h is
p r o t e in a s h
e m p a q u e n e n lo s c r o m o s o m a s
A c o n d o b le h i i c e s e
o s m e tr o s d e D N

c ro m o s o m a 1
n it u d d e 1 0 p m
a le s t ie n e n u n a lo g
m e t a f 5 s ic o s , o s c u
v e z

s e

e n

lla

r o

(c r o m

2 pm
t a n c ia

Io s

e x tre m

c ro m

o so m

a 2 1

E 1 c e n t r 6 m e r o o c o n s t r ic
la s d o s c r o m 5 t id e s h e r m

it o s is y

o so m

Ia m

e io s is

A de m

o s d e c a d a c ro m
a s s e fu s io n e n

5 s,

c i6 n

an as y

ie n

o so m

p r im

u n o s co n

a ria

q u e

e d o s t e 16 m
,

t ie n e n

o tro s

qu

e s e l p u n to

e r o s,

(G g u r a

c i6 n

la fi m
-

I)

d o n d e

a l c in e t o c o r o

c o n t ie n e

e n

d e

c a

da

u n o

d e

e v it a r q u e lo s

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Cu

a d ro 7

de

i a

i z

l 6

c ro m o s o m a s

a n o r m a lid a d e s c ro m o s 6 m ic a s IS I N (2 0 0 9 ) M a t e r ia l a d ic io n a l d e o r ig e n d e s c o n o c id o

a d d

M a t e ria l a d ic io n a l d e o rig e n d e s c o n o c id o

ce n

C e n t r6 m

c o m a (, )

S e p

a ra

e ro
e l n

c ro

s o

a s

r o

le

r m

lid

c ro m o s 6 m ic a s

de

D e le c i6 n

de

C ro m

du

D u p lic a c i6 n

fr a

S itio

in

fr5 g il

e te ro c ro m a t in a c o n s t it u t iv a

Is o
in

o s o m a d e r iv a t iv o

c ro m o s o m a

In s e rc i6 n
In v e rs i6 n

is h

H ib rid a c i6 n in s it u

a r

C ro m

a t

S ig
m

n o

d e m

e n o s (

a rc a d o r

Prdida

B ra z o

c o r to d e l c ro m o s o m a

o rig e n p a t e rn o

a t

S ig n

a m

M o s a ic o

o s

o so m

rig e n m a t e r n o

o d e m

5 s (+ )

G a n a n c ia

ps

S a t l i t e s e n b ra z o s c o r to s d e l c ro m o s o m

B ra z o

C ro
q

la r g o d e l c ro m

o so m

m o s o m a e n a n illo

S a t l i t e s e n b ra z o s la r g o s d e l c ro m

re c

C ro

ro b

T ra n s lo c a c i6 n ro b e rt s o n ia n a

T ra n s lo c a c i6 n

m o s o m a re c o m

o so m

b in a n t e

Satlite

u p d

D is o m ia u n ip a re n t a l

v a r

V a ria n t e o r e g i6 n v a r ia b le

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