Title: Introduction to DNA methylation and its impact on gene regulation
1Lecture Introduction to DNA methylation and its
impact on gene regulation Webpage http//www.mo
lgen.mpg.de/steinhof/vorlesung_ws0708/
2Lecture 6 DNMTs Eukaryotic Cytosine
Methyltransferases
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Lecture 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
4Host defense Strand discrimination in mismatch
repair (also mA)
Bacteria
DNA methylation
De novo
What for?
Eukaryotes
maintanace
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Lecture Introduction to DNA methylation and its
impact on gene regulation
5Activation of retrotransposon promoters
Genomic imprinting
DNA methylation In mammals
X chromosome inactivation
Tissue and developmental specific gene activity
regulation
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Lecture Introduction to DNA methylation and its
impact on gene regulation
6Excursus Mobile Genetic Elements
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Lecture Introduction to DNA methylation and its
impact on gene regulation
7Excursus Mobile Genetic Elements
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Lecture Introduction to DNA methylation and its
impact on gene regulation
8Excursus Mobile Genetic Elements
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Lecture Introduction to DNA methylation and its
impact on gene regulation
9Excursus Mobile Genetic Elements
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Lecture Introduction to DNA methylation and its
impact on gene regulation
10Activation of retrotransposon promoters
Genomic imprinting
DNA methylation In mammals
X chromosome inactivation
?
Tissue and developmental specific gene activity
regulation
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Lecture 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
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Lecture Introduction to DNA methylation and its
impact on gene regulation
13Human
Mouse
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Lecture Introduction to DNA methylation and its
impact on gene regulation
14Rat
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Lecture Introduction to DNA methylation and its
impact on gene regulation
15Oxtr, Pax3, Lep, Hoxb4 not methylated in Sperm
Acta1, Prf1, Mylc methylated in Sperm
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Lecture Introduction to DNA methylation and its
impact on gene regulation
16Differentiation ... 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
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Lecture Introduction to DNA methylation and its
impact on gene regulation
17Hypothesis 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
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Lecture Introduction to DNA methylation and its
impact on gene regulation
18Transfer to tissue, where it is normally expressed
- Methylated
- Non expressing in some tissue
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Lecture Introduction to DNA methylation and its
impact on gene regulation
19Eukaryotic Cytosine Methyltransferases
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Lecture 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
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Lecture 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
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Lecture Introduction to DNA methylation and its
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24DNMT1
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Lecture Introduction to DNA methylation and its
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Lecture Introduction to DNA methylation and its
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26mouse
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Lecture Introduction to DNA methylation and its
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Lecture Introduction to DNA methylation and its
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Lecture Introduction to DNA methylation and its
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31? Three oligos, more or less same picture
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Lecture Introduction to DNA methylation and its
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Lecture Introduction to DNA methylation and its
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Lecture Introduction to DNA methylation and its
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35Conservation of DNMT2
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Lecture Introduction to DNA methylation and its
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41(No Transcript)
42MeCP2 MBD1 MBD2 MBD3 MBD4
Can bind methyl CpG sequences
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Lecture Introduction to DNA methylation and its
impact on gene regulation
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44What are the mechanisms of the DNMTs?
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Lecture Introduction to DNA methylation and its
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47- How do DNMTs interfere with transcription?
- Crosstalk
- Histone
- Targeting i) chromatin
- ii) TFs
- iii) RNA
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Lecture Introduction to DNA methylation and its
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48b
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52Reminder what is RNA interference Movie
http//www.nature.com/focus/rnai/index.html
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