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 preimplantation embryo

Placental insufficiency

Blocks in differentiation

postimplantation embryo

blood cell development

Tumorigenesis

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
zygote egg sperm preimplantation embryo

(see later lectures on Epigenetic Reprogramming).

Active remodelling of epigenetic marks during differentiation.

postimplantation embryo

blood cell development

midgestation embryo

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