3. EPIGENETICS (mostly imprinting)
• Learning objectives
– Define epigenetics
– Diagram genomic imprinting (in several
different ways)
– Use the parental conflict theory to explain why
specific gene are imprinted in the male or
female parent
– Explain how patterns of Methylation of CG
dinucleotides are heritable
– Track imprinting effects through a simple
pedigree
4. Epigenetics:
Mechanisms of gene regulation that can be stably
inherited through mitosis and (sometimes) meiosis, but
can be established and released without changing the
DNA sequence
Wikipedia’s definition:
The study of heritable changes in gene activity that
are not caused by changes in the DNA sequence.
This definition is much too broad – includes all forms of
gene regulation
5. Functions of epigenetic regulation
• All our cells contain the same genes
• Different cells and tissues differ in which genes they
express.
• These differences are created and maintained by gene
regulation, not by changes in the DNA sequence (yes,
there are exceptions…).
• Some gene regulation has evolved to respond fluidly
to changing conditions within the lifetime of a single
cell.
• Other regulation needs to be stable
6. Functions of epigenetic regulation
• Regulation that needs to be stable
– Terminally differentiated cells
– Specialized progenitor cells (stem cells)
– Stably differentiated dividing cells
– X inactivation (an extreme example)
7. Mechanism of epigenetic regulation
Some of the same processes
used for other gene regulation
must be heritable but not
reversible especially regulation
that changes how the gene’s
DNA is packaged by chromatin
proteins.
– Modification of chromatin proteins
– Methylation of DNA (removed in zygote, reestablished in the
embryo and later); usually prevents gene expression.
8. What Mendel found out about peas:
6. Each seed, and thus each organism, results from one
ovum being fertilized with one pollen grain (not many, as
some had previously thought)
7. The two parents make up equal contribution to the
character
8. The effect of an allele is independent of whether it comes
from the ovule or the pollen.
Mendel’s results revealed the haploid-diploid sexual cycle
9. What Mendel found out about peas:
6. Each seed, and thus each organism, results from one
ovum being fertilized with one pollen grain (not many, as
some had previously thought)
7. The two parents make up equal contribution to the
character
8. The effect of an allele is independent of whether it comes
from the ovule or the pollen.
Mendel’s results revealed the haploid-diploid sexual cycle
10. Genomic imprinting:
For a few special genes, alleles inherited from the father are
expressed differently than alleles inherited from the mother.
Father
Mother
Offspring
11. Genomic imprinting:
For a few special genes, alleles inherited from the father are
expressed differently than alleles inherited from the mother.
Father
Allele from the father
Is inactive
Mother
Offspring
12. Genomic imprinting:
For a few special genes, alleles inherited from the father are
expressed differently than alleles inherited from the mother.
Allele from the father
Is inactive
Allele from the father
Is inactive
Father
Mother
Offspring
13. Genomic imprinting:
The identity of the allele doesn’t matter, just which parent it came from.
Allele from the father
Is inactive
Allele from the father
Is inactive
Father
Paternal
imprinting
Mother
Offspring
14. Genomic imprinting:
Here’s an example of a different gene, where the maternal allele is
always imprinted.
Allele from the mother
Is inactive
Allele from the mother
Is inactive
Father
Maternal
imprinting
Mother
Offspring
17. Genomic Imprinting
Notes:
1. The alleles behave normally in meiosis; only their expression in the
offspring is affective.
2. Dominance is meaningless… imprinted loci are effectively HEMYZTGOUS.
18. What is the function of genomic imprinting?
(Why did it evolve?)
The best explanation:
Parental Conflict Hypothesis
23. Think about how genomic imprinting works:
All of the inherited imprinting marks are erased when the
germ line develops.
A gene that’s evolved to be paternally imprinted has a sequence-tag
that says:
If you’re male, methylate this gene before you make gametes.
A gene that’s evolved to be maternally imprinted has a sequence-tag
that says:
If you’re female, methylate this gene before you make gametes.
24. Imprinting has evolved to a state where both parents’
interest are roughly in balance.
But it causes problems if something goes wrong with normal
inheritance:
a.) Defective allele from the non-imprinted parent
b.) Deletion from the non-imprinted parent
c.) Both alleles inherited from one parent (‘uniparental disomy’)
b.) and c.) are especially bad because imprinted genes are
often clustered together on one chromosome.
25. Imprinting causes problems if something goes wrong
with the normal inheritance:
One segment of chromosome 15
includes genes that are paternally
imprinted and genes that are maternally
imprinted.
26. Imprinting causes problems if something goes wrong
with the normal inheritance:
One segment of chromosome 15
includes genes that are paternally
imprinted and genes that are maternally
imprinted.
Inherit deletion
from father
Inactive alleles
From mother
(M-I)
Prader-Willi
Syndrome
Inherit deletion
from mother
Inactive alleles
From father (P-I)
Angelman
Syndrome
