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Condensacion del DNA

Empaquetamiento del DNA en

la Cromatina

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3-99 JHW

  HROMATIN

HROMATIN

  Chromatin•  Histone structure•  Nucleosome

•  Chromatin fber•  Gene repression•  Histone acetylation•  Chromatin transcripti•  Gene expression cont

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DNA compactioncompaction  in a human nucleus

1bp (0.3nm

!0"000 nm

30nm

11

nm

Compaction o# DNA $% &istones Compaction $% c&romosome sca'old nuclear matri)

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Nuclear - chromosome compaction

Compaction $% c&romosome sca'old nuclear matri)

radial loopc&rosomosome model

!µm

   !   0     µ  m

chromatidchromatid

  m   i   t  o   t   i  c  c   h  r  o  m  o  s  o  m  e

+ 2M NaCl

histones

+ 2M NaCl

histones

Mitosis

DNA loo

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HISTONES

are

 highly conserved,small, basic proteins

H!

H*+

H*A

H3

H,

&eli)

aria$le

consered

Histone acetylation

is a reersi$le modicationo# l%sines in t&e N-terminio# t&e core &istones.  Result/• reduced $indin to DNA• desta$ili1ation o# c&romati

2iner &istone

Core &istones

N

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  ore

Histones

 4&e $asic structure o# A22  core &istones is t&e same/•  ! lon &%drop&o$ic alp&a-&eli)"  $ordered $%

•  * s&ort &%drop&o$ic alp&a &elices  t&at #orm pairs•  H*A - H*+ and H3 - H,  5&ic& interact.

Reerences! Moudrianakis et al. PNAS 88, 10138 (1991);  PNAS 90, 10489 (1993); PNAS 92, 11170 (199)

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Histone octamer assembly

H3"H#tetramer

H2$"H2dimer

Histoneoctamer

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Histone octamer forms a ramp for

DNA

H, 5&iteH3 reenH*A li&t $lueH*+ dar $lue red/ 6 (ar" l%sorane/-7H (ser" t&r

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Histone octamer orani!es "#$ bp of

DNA

•  Eac& core &istone dimer  &as 8 DNA $indin sur#aces  t&at orani1e 3 DNA turns

•  4&e &istone octamer  orani1es !,: $p o# DNA  in ! 3, &elical turn o# DNA/,; nm o# DNA pacaed in a disc o# 8 )!!nm

< 8 nm =

  <

   !   !  n  m 

  =

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  hromatin

fibers

+ char&ed N termini($ind DNA on nei$orin

nucleosomes

hi&hly acetcore hi

(especiall% H3 a

30 nmchromatin fber

1'

•  H)GH le*el o histone H1 •  Reduced le*el o hist

•  N &ene transcription •  Gene transcription