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Introduction to DNA methylation and its impact on gene regulation

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Lecture. Introduction to DNA methylation and its impact on gene regulation. Webpage: http://www.molgen.mpg.de/~steinhof ... Excursus: Mobile Genetic Elements ... – PowerPoint PPT presentation

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Title: Introduction to DNA methylation and its impact on gene regulation


1
Lecture Introduction to DNA methylation and its
impact on gene regulation Webpage http//www.mo
lgen.mpg.de/steinhof/vorlesung_ws0708/
2
Lecture 6 DNMTs Eukaryotic Cytosine
Methyltransferases
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
3
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
4
Host defense Strand discrimination in mismatch
repair (also mA)
Bacteria
DNA methylation
De novo
What for?
Eukaryotes
maintanace
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
5
Activation of retrotransposon promoters
Genomic imprinting
DNA methylation In mammals
X chromosome inactivation
Tissue and developmental specific gene activity
regulation
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
6
Excursus Mobile Genetic Elements
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
7
Excursus Mobile Genetic Elements
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
8
Excursus Mobile Genetic Elements
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
9
Excursus Mobile Genetic Elements
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
10
Activation of retrotransposon promoters
Genomic imprinting
DNA methylation In mammals
X chromosome inactivation
?
Tissue and developmental specific gene activity
regulation
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
11
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
12
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
13
Human
Mouse
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
14
Rat
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
15
Oxtr, Pax3, Lep, Hoxb4 not methylated in Sperm
Acta1, Prf1, Mylc methylated in Sperm
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
16
Differentiation ... Methylation Differentiation
is regulated by mechanisms that are conserved
between organisms with methylated genomes, such
as vertebrates, flowering plants, fungi etc, and
those whose genomes have little or no methylation
(C. Elegans, Drosophila) -gt DNA methylation is
not the main regulatory process? mC down -gt
defect later than expected in development (weak
argument ? ... )
Observation Plasmid with arbitrary patterns of
cytosine methylation Transfection such that it
integrates into the host genome Up to 80 cell
divisions pattern stable
Tim Bestor
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
17
Hypothesis Histone modifications and chromatin
structure other than DNA sequence and methylation
are inherited during S Phase without ongoing
signal. Histone modifications are consequences of
active transcription Histone modifications do
not convey regulatory information they are
slaved to the activity of sequence specific DNA
binding proteins
Tim Bestor
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
18
Transfer to tissue, where it is normally expressed
  • Methylated
  • Non expressing in some tissue

VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
19
Eukaryotic Cytosine Methyltransferases
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
20
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
21
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
22
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
23
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
24
DNMT1
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
25
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
26
mouse
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
27
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
28
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
29
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
30
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
31
? Three oligos, more or less same picture
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
32
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
33
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
34
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
35
Conservation of DNMT2
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
36
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
37
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
38
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
39
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
40
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
41
(No Transcript)
42
MeCP2 MBD1 MBD2 MBD3 MBD4
Can bind methyl CpG sequences
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
43
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
44
What are the mechanisms of the DNMTs?
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
45
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
46
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
47
  • How do DNMTs interfere with transcription?
  • Crosstalk
  • Histone
  • Targeting i) chromatin
  • ii) TFs
  • iii) RNA

VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
48
b
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
49
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
50
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
51
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
52
Reminder what is RNA interference Movie
http//www.nature.com/focus/rnai/index.html
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
53
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
54
VI
Lecture Introduction to DNA methylation and its
impact on gene regulation
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