? ? ? ? ? (epigenetics) ?????? ???

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? ? ? ? ?(epigenetics)?????? ???
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? ? ? ?

• 2000???,????????????On the Generation of
  Animals???????????(the theory of
  epigenesis),???????,???????????????????

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? ? ? ?

• 1939?,???? Waddington CH ??????????????epiheneti
  cs????,
• ??1942???????????????,??????????????????????

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• 1975?,Hollidy R ?????????????????
• ???????????????,????????????????????,?????????????
  ??????????????,?????DNA?????,??????????DNA????????
  ?

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? ?

• ?????
• ?????DNA???????????????????,??????????????????????
  ??????????
• ????
• ???????????DNA????????????????,DNA
  ????????,???????????????????,??????????????????(??
  ??,???,???,DNA???,???????? ), ?????????????

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• Definition of Epigenetics
• Any changes in gene expression resulting from
  either a DNA and chromatin modification or
  resulting from a post post-transcriptional
  mechanism. However, it does not reflect a
  difference in the DNA code?
• A unifying definition of epigenetics (Adrian
  Bird, nature, 2007)
• the structural adaptation of chromosomal regions
  so as to register, signal or perpetuate altered
  activity states.
• This definition is inclusive of chromosomal
  marks, because transient modifications associated
  with both DNA repair or cell-cycle phases and
  stable changes maintained across multiple cell
  generations qualify.

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? ?

• ????????
• ????,????????????????,????????????
• ??????????,????????????????????
• ??DNA?????????DNA????????

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? ?
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? ?
???????
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? ?
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? ?
DNA????
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? ?
??????
??????
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? ?

• ??????
• ?????????????,????????,???????????????????????????
  ??????????????????????????
• ?????????????????????????DNA??????
• ????????????????

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? ?

• ??????????

• ????????
• ???????RNA
• ??RNA(miRNA)
• ??RNA
• ?????????

• ????????????
• DNA???
• ????
• ???????
• ?????

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Quiz, J. nature. 2006
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???????
1
DNA ???
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??DNA???

• DNA???(DNA methylation)????????
  ??????????????,?????? DNA??????5?????????????,????
  ?????5?????(5-methylcytosine,5mC)?

S-??????
????????
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?????a/a????????????AVY/a???????????????,?????
????????,???????????????????????????,?????????????
?
???????????????????????????????????,??????????
???????????????????????????????????????????IAP??Cp
G???????????????,?????????????????????????,???????
??
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??DNA???
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??DNA???

• ????????5mC???????2-7,?70?5mC???CpG?????
• ??????5?????, CpG???????????????,????CpG?????????
  CpG?(CpG islands),????500-1000bp,?56??????????
• ??????(????)??CpG???5mC???????????DNA????
• DNA?????????????
• ???????????????
• ???????????????????????

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??DNA???
3
5
Rb??

• CpG???????5??????
• ??????CpG???????????,????????????????????
• ??????????(????)?CpG????5mC?????????????????DNA???
  ???DNA??????????????

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??DNA???
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??DNA???

• DNA???????????
• DNA???,?????DNMT1????,????????????(????????,95)
• ?????????????????????,????????????,???????
• DNA??????????????
• DNA??????????????
• RNA???????????????
• ?????????????????????????

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??DNA???

• DNA????
• ??????
• ?????????
• ??????????????????????????????

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??DNA???
?????DNA????
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Manel Esteller, nature, 2007
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??DNA???
DNA??????
DNA?????
DNA????????
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???????
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???????

• ??????????????????
• ???? N????????????????,?????????,??????????,??????
  ?????????????
• ??????????????,?????????????,???DNA???????,???????
  ?????????????,????????????????????????????

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???????
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???????

• ???????
• ???-- ??????????????,??????????H3?H4? Lys ????
• ???-- ???H3?H4? Lys ? Asp ???,?????????,??????????
  ?,????????????????
• ???-- ??? Ser ??,??????????
• ???-- ???C?Lys??,???????
• SUMO(???????)?-- ????????
• ????

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???????

• ?????????????????????????????(histone
  code),????????????,????????????,??????

Bryan M. Turner, nature cell biology, 2007
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???????
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???????

• ?????(chromatin remodeling)??????????????
• ???????????????????????????????????????????
• ??????????(????????????)?????????,????????????

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???????

• ???

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???????

• ??????????DNA??????????
• ?????DNA??????,???????????
• ???????
• ??????????????????DNA???
• ?????????????,????????????????
• ????????
• ??????DNA????????
• ?????????????

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???????

• ??????????????????
• ??1?????????????DNA ??(DNA?????????????), ??,
  ???????????????, ?????????????????, ????????????,
  ??????????? (??)
• ??2????????????????, ??????, ??????????, ???
  ????????, ????????????????? (??)

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???????
????????(??????ATP???)
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???????
ATP??????????
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???????

• ???( boundary elements)????????????????????(
  insulator elements)?
• ????????????
• ???????????????
• ?????????(CPE)?
• ????????????????????????,?????????????,??????????

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??RNA??

• 1995,RNAi???????????
• 1998,RNAi????????
• 1999,RNAi????????????????????????????????RNAi???
• 2001,RNAi??????????????????????RNAi
  ???Science??2001????????????
• ??,????,???????????????????

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??RNA ??

• RNA??(RNAi)??????????????RNA???mRNA???????????????
  ???
• ??RNAi????????,????????????(post-transcriptional
  gene silencing, PTGS )?
• RNA??????????????????

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??RNA ??

• siRNA
• siRNA??21-23nt?????,????mRNA????,??????2???????3
  ???
• siRNA???RNAi ???????,?RNAi???????????siRNA???????
  ??????????????

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??RNA ??
siRNA???RNAi
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??RNA ??

• siRNAi ???
• ?????????
• ???
• ????
• ????
• ???RNAi?????
• ??????ATP???

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??RNA ??

• miRNA
• ??21-25nt???????RNA ,5'????????,3'????,?????????7
  0-90????????RNA????Dicer???????
• ???????????????????? ?
• ??

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??RNA ??
siRNA???RNAi
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??RNA??
 
               
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??RNA ??
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??????????

• ?DNA?????????????????RNA????,???????X?????????????
  ?
• ?????X??????????DNA????????????????

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? ? ? ?

• ??
• ??????(parent imprinting)
• ????????????????,??????????(DNA??????????????????
  ??????)?????DNA?????????
• ??
• ????????????????????,??????????????????????,??????
  ??????????????????
• ????????,????????????,????????

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? ? ? ?
? ?
? ?
?
?
?????
????
?????
????
?????
????
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? ? ? ?

• ??????????
• ???????????????????????
• ?? Igf-2 ????????????????,???????????,????????
• ??????????????,?????????????????

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? ? ? ?

• ??????
• ?????
• ?????????,????????
• ?????
• ?????
• ???????????????????????
• ????????
• ????????,DNA????????????????????????????,?????????
  ?????

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X?????

• 1961?M.F.Lyon??????????????????X?????????????????
  ,??????????????????????????????????????,???X??????
  ??????????,?????????????X???????????????????
• 1996?G.D.Penny???X????Xq13.3?????X????(
  X-inaction center,Xic),X-???Xic??????,???????????

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X?????
X??????????
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X?????

• ??X??????????
• ??X?????
• ???H4?????
• CpG???????

????
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Thank You For Your Attention !