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Regulation of Gene Expression in Eukaryotes

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Title: Regulation of Gene Expression in Eukaryotes


1
????
  • ??????????

Regulation of Gene Expression in Eukaryotes
2
  • 1970?,????40(simian virus 40, SV40)???????????????
    ?,?????????????????
  • 1975?D. Pribonow??T7??????
  • 1982?C. Benoist?P. Chambon???SV40?????????
  • 1983?,W.S. Dynan?R. Tjian????????????AP1?
  • 1986?,J.Clarke?Chambon??????????SV40????????????
  • 1990??,????-???????????????

3
(No Transcript)
4
(No Transcript)
5
???
??????
Control of Transcription Initiation
6
?????????
????
???? ????? mRNA??
7
????????????
  • ????????
  • ???????????????
  • ?????????????

8
??????????????????DNA????
  • ??????????DNA?????????DNA????????????????????,????
    ???????????????????????
  • ???????-???????????????????,?????????????????? ?

9
  • ??????????(cis-acting elements)?????(promoter)????
    ??????????? ?

10
(?)?????TATA?/????CpG??????????????
  • ????????????????(transcription initiation
    site?transcription start site)????????????RNA?????
    ??????DNA???
  • ??????????(core sequences)??????????2535
    bp?,?????TATA??,???TATA?(TATA box),?????TATA???TAT
    AAAA???TATA????????????,?RNA???II?????????????

11
  • ??????????????????,?????(initiator,Inr),?????????
  • ????????(5?)Y-Y-A1-N-T/A-Y-Y-Y(3?)Y?????C?????T
    ,N??????,T/A??T?A?

12
  • ????????????????????,??????5????mRNA?
  • ????????????,?????????????
  • ????TATA?????,?????????100 bp???20?50?????CG??,???
    CpG?(CpG island)?

13
(?)?????????????????
  • ???????(promoter-proximal elements, ?upstream
    promoter elements)?????TATA????DNA??,???????,?????
    ????TATA?????RNA??????????,????????????,??????????
    ??????
  • ??????

14
(?)????????RNA???II???
???(enhancer)
?????????????,??????????????DNA??????,?????????(u
pstream activator sequences, UASs)?
  • ?????????????????????

15
  • ???????
  • ????????????,???????????????,?????????????????????
    ?
  • ?????????????????,?100 nt?50 000nt,???????????????
    ???

????????????????????
16
(?)???????????
?????????(silencer)
?????????????,???????????,???????????
??DNA?????????,???????????????????,???????????????
???
17
???????????????????????
????(transcription factors)
18
  • ??????

RNA???????????????????,?????????????,??3?RNA??????
??????
?????????????????????????????
??????
  • ??????????????,?????????????

19
(?)?????????DNA???
  1. ??-??-??????DNA??????

????? (homeodomain,HD)
??-??-?? (helix-turn-helix,HTH)
20
2. ??????????DNA???????
C2H2???(Zinc finger)
21
????ß??
Zn2
a??
DNA??
22
3. ?????????DNA??????????
?????(leucine zipper)
23
4. ????-?-????????DNA??????????
????-?-?? (basic helix-loop-helix,bHLH)
24
5. ???????DNA
??????DNA????,?????-?????DNA??????????????????????
,??-????,??????????,????DNA???????????????
25
(?)?????????-?????????
??????bHLH?????????????(?)??(?)?????(?)???(heterod
imer)????????????????
????????????????????????????,????????????RNA??????
?????????????????
26
??????????????3?
  • ???????????(glutamine-rich activation domains)
  • ??????????(proline-rich activation domains)
  • ??????????(acidic activation domains)?

27
????(repressor protein)
????DNA???,??????????????????
????????????DNA???,???????-????????,??????????????
?????
28
????????????????????
  • ????????????????
  • ?????

???????????????????????? ??????????????????????
????
29
????????????????????????????????
  • ??????????????????????,???????????????????????????
    ???
  • ????????????,????????????????,???????????????????
  • ??????????????????????????????????DNA?????????????
    ??????

30
(?)????????????????
????????????????????????
  • ????(heterochromatin)????????
  • ????(euchromatin)??????????????,????????5-???1000
    nt????????(hypersensitive sites)?????????????????
    ??,????????????????????????????

31
??????????????????????????????
  • ?????????(H2A,H2B,H3,H4)??????????????,???????????
    ??,?????????????????????
  • ????DNA?CpG??(CpG?)??????????5-??????????,????????
    ???????????????

32
  • ?????(chromatin remodeling)

??????????????????????????????????????????????????
???????????? ?
  • ????????

33
?????
34
  • ??????

????????????????????
???????????(histone acetyl transferases,
HATs),?????????(histone acetylase)????????????????
???????,????????DNA?????
35
?????????????????????????????????????????
??????????(histone deacetylase)?????????,????????
??????
36
(?)?????????RNA????????????????????
RNA???II????????????????????????????????
?????????????UASs??? ??????????????? ??????(coac
tivator)?/????(medicator)???????/RNA???II?????????
?????????????
37
??????????????,?????????????????,?????????????????
?????
??,??????????????????,?TFIID?TFIIA,?????????????,?
?????????????(transcription initiation
complex),?????
38
(No Transcript)
39
??????????????????????RNA???????,???????
???(twisting)
???????DNA???????,???????????RNA?????,
??????????????/?????????????RNA???????
40
???(sliding)
?DNA??,?????????DNA?????????,?????
???(looping)
??DNA??????????,???????RNA?????????,???????????/??
???????
41
????????????????????????????????,???????????,?????
-????????DNA???????????????(hormone response
elements, HREs),???????????????,?????????????
42
???????????
?? ??????
???(androgen) GG(A/T)ACAN2TGTTCT
????? (glucocorticoid) GGTACAN3TGTTCT
??? (retinoic acid) AGGTCAN5AGGTCA
???D (vitamin D) AGGTCAN3AGGTCA
????? (thyroid hormone) AGGTCAN3AGGTCA
????A (retinoid X) AGGTCANAGGTCANAGGTCANAGGTCA
43
(?)?????????????????
??????????????????
??????????????????DNA????
?????????????????DNA??????,???????????????????????
,???????????
44
??????????????????
????????????
??????????????(repressive chromatin remodeling
complexes)
????????????
45
? ? ? ?????
Posttranscriptional Controls
46
??????mRNA 5?????3??????????
?????,??????mRNA??5?????3???poly(A)??? ?
5?????3???poly(A)??????????
47
5????????
??????mRNA??????????
???mRNA??????????????,????????????????
???mRNA??????????
?5???????????mRNA???????????? ?
48
poly(A)????
poly(A)?????????????,??mRNA????,??????????????????
mRNA???poly(A)?,??????????mRNA??,?????mRNA??????
49
??????????????????????
?????????????????????(alternative RNA
splicing)??,?????????????????mRNAs,??????????
50
???????mRNA??????
mRNA
Pre-mRNA
????mRNA
51
????????????????????????? ??????????????????????
RNA?????????
????????????????
?????????????????????????????????????
??????????????????????????????????
52
??RNA??????RNA???????
??mRNAs???????(editing)?
????????????4?U??,???????????????
?????????????????????????RNA??,?3????? poly(U),
?5?????mRNAs????????,?????RNA(guide
RNA)???RNA???????????,???3???U???????mRNAs?
53
??RNA??????????
?????1/5?????mRNAs????????????mRNAs??1??????mRNA?
???????????????,????????????(nuclear export
receptors)????9nm??????
????RNA?????????????????
54
????RNA?????????????
????mRNA???????,????????????????????????
????????????????????????
55
?????????mRNA?3??????(3?untranslated region,
3?UTR)?
  • ?????

mRNA?????????????????(motor proteins)?,?????ATP???
????????????????,??????????(anchor proteins)???
  • ?????

mRNA????????????,???????????????
  • ?????

mRNA????????????????,??????????????
56
mRNA???3???????
57
??mRNA??????????????
????????mRNA???????????????????
???????mRNA??????????
??????????????????????????
??????????mRNA ????????????
58
????mRNA???????,????mRNA?????????
  • poly(A)???????????
  • mRNA??????????,???????poly(A)??????,????30?A?,5???
    ???,mRNA????????
  • ??mRNA???3?UTR????????????????,?????poly(A)??????

59
  • ???????????????
  • ??poly(A)???mRNA??????????????mRNA???3?UTR????????
    ?????

??
??????(transferrin receptor, TfR) mRNA??
3?UTR??(stem-loop)???????(iron-response
element,IRE)?
60
IRE-BP???????mRNA??????
61
?????poly(A)???????????
??????,???poly(A)?????????????
???????????????
?????????mRNA???3'????10-30????(A),???????????????
??????????,?????mRNA ????????,poly(A)?????????mRNA
??,????????????
62
?????????mRNA???????mRNA????
???????mRNA?? (nonsense-mediated mRNA decay, NMD)
?????????????????UAA?UAG?UGA??????????????????50
nt??,mRNA??????????????????????????(premature
termination codons, PTC),????????????????????
63
???????mRNA???
64
??
  • ????????mRNA???????????????? ,??mRNA??????????????
    ?????? ?
  • NMD?????????????,????????????DNA??????????????????
    ??
  • ????????????????,?????????mRNA?NMD??????,?????????
    ??????

65
??RNA?????????????
RNA??
??????????????RNAs (small RNAs)??????????????????R
NAs?mRNAs(???3?UTR)????,??mRNA????????,?mRNA??????
???????(silence)?
??
???????????????????????????RNA??????????????? ?
66
miRNA ?siRNA??mRNA????
67
???
? ? ? ?
Translation Control
68
???????????????????
???????????????,???(??)????eIF-2(eukaryotic
initiation factor,eIF-2)??????
69
(No Transcript)
70
????mRNA 5??3????????????????
????????????mRNA?5????????,??????????????mRNA???3?
UTR,????3?poly(A)??5???????????????
71
IRE-BP????mRNA?????
????
72
??????mRNA??????????
  • ????????????,??????????????????AUG??????,?????AUG
    ,????????????(leaky scanning),?????mRNA???????????
    ???????????????????,????????????????????????????

73
  • ????????(upstream open reading frames ,
    uORFs)???mRNA ???,?????AUG???(5?UTR)??????AUG,???
    ?????????????????????,???????????????????????

?? ???????,???AUG??????????AUG????????????,??????
????????????????
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