epigenetics Flashcards
what is epigenetics
Epigenetics = (part of) the answer to understand phenotype complexity in the ‘post-genomics’ era
- study of heritable changes in gene activity or expression (which can be influenced by the environment) that do not involve alterations to the underlying DNA sequence
- (EPI) genetics – > “over” our genes
- Epigenome = Histone modifications + DNA methylation + Non-coding RNAs
what are the 2 Modern definitions of epigenetics and who wrote them
Holliday 1994
- “The study of the changes in gene expression which occur in organisms with differentiated cells, and the mitotic inheritance of given patterns of gene expression”
Wu & Morris 2001
- “The study of changes in gene function that are mitotically and/or meiotically heritable and do not entail a change in DNA sequence”
what are Quantitative traits
phenotypes that depends on the actions of many genes + the environment
importance of epigenetics
- Development
>Cell type + function
>Seasonal + temporal variation
>ageing - Disease
>Inheritance
>Epidemiology
>Therapeutics - Evolutionary biology
>Adaptation
>Variation
>Domestication
>Phenotypic plasticity
explain the origin of epigenetics, who done it and what its shown by
Conrad H. Waddington - Waddington’s Epigenetic Landscape (1953)
- “The branch of biology which studies the causal interactions between genes + their products, which bring phenotype into being”
- Increasing irreversibility of cell type differentiation
- Cell fates are established & maintained by epigenetic marks
3 Epigenetic modifications
Histone modification
DNA methylation
Non-coding RNAs
explain Histone modification
- Histones = proteins that DNA wrap themselves around (can be modified – make the DNA difficult to read)
- Around 100 different histone modifications known
- Euchromatin = active state
- Heterochromatin = silenced state
- Different outcomes depending on:
>The modification itself
>The genomic location of the modification
>The presence of other modifications on the same genomic location
purpose of histone tails
interact with other molecules (e.g methyl, acetyl) and can spool and unspool the DNA and make it easier to read (gene expression)
how to Characterise histone amino acid tails
1-2 (e.g H3) = histone ID
3 (e.g K) = amino acid
4-5 (e.g 27) = AA position on tail
6-8 (e.g me3) = chemical modification
how can the epigenome be reprogrammed (histone modification)
after fertilisation stage, some modifications are switched on and switched off during embryo development – different parts of the genome are being expressed at different times – imply histone modifications are important in development of embryo
- Temporal variation in mammals = epigenetic reprogramming
what is DNA methylation and what enzyme is involved in mammals
Addition of methyl group to the carbon of cytosine - usually prevents transcription
DNA methyltransferase
explain DNA methylation patterns
- Mostly at Cytosines in the genomic context -CG- (also called CpG)
- Other genomic contexts: -CHH- and - CHG- (H = A, T or C)
- Genomic regions rich in CpG prone to methylation = CpG islands (often associated with promoter regions)
- Differential patterns and types of methylation in different species
- different body parts have different methylation percentage – majority of placenta tissue is methylated
- Methylation can have different effects on gene expression depending on its location (e.g. promoter regions or gene bodies)
how does DNA methylation effect evolution
Relative methylation of CpG motifs is positively correlated with genome size
effect of DNA methylation in promoters
- DNA methylation in promoters is generally repressive (gene silencing) - impedes the binding of transcription factors e.g.
>colour production in tomatoes – methylated promoters in tomato genes leads to difference in pheynotype (no redness)
>aberrant methylation in cancer protooncogenes means that the protein will not be expressed therefore no uncontrolled cell growth
effect of DNA methylation in gene bodies
has a more complex relationship with gene expression
- It may inhibit gene expression e.g. no petal formation in snap dragon
- But in some cases, gene body methylation stabilises / induces transcription e.g. increased oncogene expression leading to uncontrolled cell growth
