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Samenvatting Regulome HC3
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College-uitwerkingen van het onderdeel regulome, hoorcollege 3. Inclusief afbeeldingen
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REGULOME – Lecture 3Regulatory layers I
Part 3: Chromatin, DNA methylation, ChIP-seq (ChIP-seq data analysis I)
The genome looks rather inefficient. Only 1,5% is protein coding. The rest is spacer sequence or
regulating sequence.
Transcriptional regulation
Every cell has the same DNA (genome).
But: human cells can look quite different, have different functions while having the same DNA = same
blueprint. The regulation therefore really matters beside the information that sits in our genes.
Different expression --> different cell type
How is this regulated?
Regulation is highly redundant
Small amount of protein coding genes
Big amount of regulatory sequences (high abundance)
Genes & Gene Regulation
Gene = genomic substring that encodes HOW to make a protein
20,000 - 25,000 genes in human, same amount as in bacteria
Genomic switch = genomic substring that encodes WHEN, WHERE and HOW MUCH of a protein to
make
1,000,000 genomic switches (they control genes) in human
Much more than in bacteria --> more complicated organism
Active genomic switches determine the cells activity.
Multiple layers of switches
, Epigenetic markers on DNA (methylation), proteins interacting with DNA (chromatin)
DNA methylation
Methylation occurs on cytosines
Methylated C can still basepair with G so the genetic code remains the same.
The change is another signal that might be recognized by other proteins (activators instead of
repressors)
Methylation sticks out of DNA helix so easy to detect
Methylated DNA is a signal for repression/inactivity
Methylation on DNA --> heterochromatin (dense packed)
Genomic distribution of DNA methylation
C's: only 4% is methylated
CpGs: 75% is methylated, because methyl transferases recognize CG
98% of the genome
1 in 100 bp is CpG, majority methylated
Inactive
<2% of the genome
CpG islands: 1 in 10 bp is CpG (often in promotors), high overrepresentation of CpGs. Most
unmethylated --> active!
Why are only CpG islands mehtylated?
Because of the maintenance of methylation when the cell devides. Methylation on CpG-island
--> one C to both cells --> both cells maintain methylation after cell division
Always palindromic motifs for maintenance of epigenic motifs
Chromatin structure and function
Higher regulatory levels than methylation and acetylation
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