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L5 Chromatin and Gene Expression
How can identical twins have different natural hair colour?
How can a single individual have two different eye colours?
How can acquired traits be passed on to offspring?
How do stem cells know their fate?
Epigenetic Modifications:
1
...
Histone modifications (Me and Ac)
3
...

 Methylated cytosine are often found in CpG islands
 CpG dinucleotides are palindromic
o 5’ CpG 3’
o 3’ GpC 5’
 Methyl group on outside of phosphate backbone allows the chromatin to be remodelled
...

 DNA methylation and Histone PTMs combine to help compartmentalise the genome into domains of
transcriptional potentials
o EUCHROMATIN - ACTIVE
 High histone acetylation
 Low DNA methylation
 H3-K4 methylation
o HETERCHROMATIN - INACTIVE
 Low histone acetylation
 Dense DNA methylation
 H3-K9 methylation
 During replication the daughter strand wont be methylated
...


All Paternal DMRs methylated – H19 OFF Igf2 ON
o DMR1 is a silencer inactivated by methylation
o DMR2 is an enhancer that is activated by methylation
Maternal DMR s hypo-methylated – H19 ON, Igf2 OFF
o CTCF binds DMR
o Downstream enhancer engaged for H19 expression
o DMR1 silencer of Igf2 active
o DMR2 enchancer of Igf is inactive
Parent-of-origin expression imprints must be
correcctly set in the gametes every generation
Failure to re-set correctly leads to development
disorders in next generation
Primordial germ cells are demethylated and de
novo methylation occurs in meiosis

Pader-Willi Syndrome
 Deletion
 Obesity, short, small hands/feet, unsual facial features, mild mental retardation
 Compulsive overeaters
 Failure to imprint  wrong level of maternal or paternal gene expression – Paternal imbalance
...


If a gene is methylated in a somatic cell it will then always be methylated there is no DNA demethylate-or so can’t
remove it
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Roles of DNA methylation:
 Transcriptional silencing
 Protecting the genome from transposition
 Genomic imprinting
 X inactivation
 Tissue specific gene expression
Control of expresssion through epigenetic modification
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OFF
DNA Methylation
H3K9me3
H3k27me3
Tightly wound Chromatin

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ON
No DNA methylation
H3K4me3 (especially at
promoters)
H3K36me3
Looser structure – DNA binding
proteins (transcription factory)
Histone variantss

If chromatin remodellors meet methylated DNA then it will rewind the DNA, even if the transcription factor was
bound

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