Epigenetic control is important throughout development

zygote
egg
sperm

preimplantation embryo

postimplantation embryo

blood cell
development

midgestation
embryo

Epigenetic control is important throughout development, and goes wrong in disease.

Imprinting disorders
Infertility

Early embryonic lethality

zygote
egg
sperm

Blocks in
differentiation

Placental
insufficiency

postimplantation embryo

blood cell
development

Tumorigenesis

preimplantation embryo

midgestation
embryo

Germ cell tumours

Sometimes, even genetically identical people

i.e. identical twins, are discordant for disease!

Identical twins are genetically identical sometimes

epigenetically different?
Identical twins are made when an early embryo splits into two, they
were made from the same egg and same sperm = genetically
identical to each other

Identical twins are genetically identical sometimes

epigenetically different?
Identical twins are made when an early embryo splits into two, they
were made from the same egg and same sperm = genetically
identical to each other
Identical twins can have different appearances (e.g. 30%
discordant for height)
Sometimes, genetically identical twins both carry a disease gene,
but only one has the disease phenotype
Why?
Environment?

Definitions of epigenetics
Use of the term epigenetics and its definition has changed throughout history.
Conrad Waddington, 1942 study of epigenesis; how genotypes give rise to
phenotypes in development
Robin Holliday, 1990 - temporal and spatial control of gene activity during
development of complex organisms.
Our current definition (similar to Art Riggs et al, 1996):
Epigenetics is the study of mitotically heritable changes in gene expression that occur
without changes in DNA sequence.
Other current definitions do not include the necessity for the epigenetic changes to be
mitotically heritable.
We wont be absolutely strict on the requirement of heritability.

Mitotic heritability of epigenetic state helps to maintain cell identity.

Heritability of epigenetic state ensures

the same sets of genes are
expressed in daughter cells
tissue homogeneity

Mitotic heritability of epigenetic state helps to maintain cell identity.

Lack of heritability of epigenetic state

would result in tissue heterogeneity

Heritability is countered by periods when epigenetic marks are removed.

Epigenetic reprogramming in germ
cells and early development
(see later lectures on Epigenetic Reprogramming).

zygote
egg
sperm

preimplantation embryo

postimplantation embryo

blood cell
development

midgestation
embryo

Active remodelling of epigenetic

marks during differentiation.

Acknowledgements

Glow at the Danish language Wikipedia [GFDL (http://www.gnu.org/copyleft/

fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via
Wikimedia Commons