Транскриптомика и эпигеномика
Learning objectives
This lactose metabolism system was used by François Jacob and Jacques Monod to determine how a biological cell knows which enzyme to synthesize. Their work on the lac operon won them the Nobel Prize in Physiology in 1965
lac-operon – example of a “classical” (NOT epigenetic) gene regulation
Part 1. Biological background.�Epigenetics
У каких организмов есть эпигенетическая регуляция и зачем она нужна?
A new challenge for multicellular organisms
Levels of regulation of gene expression
DNA is not the only factor
Genetics vs epigenetics
There are at least two forms of information in the cell:
• Genetic information: provides the building block for the manufacture of all proteins needed for the cell functional activity;
• Epigenetic information: provides additional instruction on how, when and where these information should be used.
What is epigenetics?
Molecular basis of epigenetics
Types of epigenetic regulation
DNA accessibility (DNA packing)
Packing of DNA is required to fit into the nucleus
Molecular Biology of the Cell, 4th ed.
DNA methylation
Histone modifications
Epigenetics kicks genetics
A bit of history
Waddington’s epigenetics landscape (1942):
When the term was invented the physical nature of genes and their role in heredity was not known; he used it as a conceptual model of how genes might interact with the environment to produce a phenotype.
Multicellular organisms: one genome – different epigenomes
During morphogenesis a single fertilized egg cell – the zygote – divides and the resulting daughter cells change into all the different cell types in an organism by activating some genes and repressing others.
Chaudry, A. (2004). Stem Cell Bioengineering
Example: X-chromosome inactivation
Example: genetic imprinting
In mammals, some gene (imprinted genes) bypass epigenetic reprogramming keeping the epigenetic profile. As a result only one copy of an imprinted gene is active in normal individual.
http://learn.genetics.utah.edu/content/epigenetics/imprinting/
Reversibility of epigenetic changes
Epimutations are more easily reversible than classical mutations: giving evolution more flexibility – selection for epigenetic variability and giving us a change to be not only what our genes are
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Part 2. Biological background.�Epigenetic mechanisms: DNA methylation
Learning objectives
Function of DNA methylation: �CpG islands
- (C+G) >= 50%
- Obs CpG / Exp CpG >= 60%
- Length >= 200 bp
DNA methylation and cancer
Igf2 imprinting
Igf2 (Insulin-like growth factor 2) is a major fetal growth factor