Epigenetics Flashcards
Define epigenetics
The study of reversible heritable changes in gene function that occur without a change in the sequence of DNA
What did Bird propose?
A modern definition that avoids the requirement for heritability in epigenetics
What are the mechanisms of epigenetics?
- histone modification and chromatin remodelling
- DNA methylation
- Non-coding RNA mediated regulation
Which nucleotides are purines?
A and G
Which nucleotides are pyrimidines?
T and C
What is an epigenetic landscape?
A metaphor in which valleys and ridges illustrate the epigenetic landscape that guides a pluripotent cell to a differentiated state, represented by a ball rolling down the landscape
What are some examples epigenetics play roles in?
Developmental process, whereby an undifferentiated cell undergoes differentiation towards it final state.
E.G. lymphoid/myeloid development, T-helper, neural stem cells and muscle differentiation
What is the histone code hypothesis?
Modifications of histone tails act as epigenetic marks that control the expression or replication of chromosomal regions
What does DNMT1 do? What does DNA demethylase do?
Follows the replication fork adding methylation marks to newly synthesized DNA - re-established histone modifications.
DNA demethylase takes off replication marks
What is DNA methylation?
An epigenetic gene regulation.
In vertebrates, 5-methylC residues within the CpG dinucleotide. 5-hyrdomethylC, 5-formylC and 5-carboxylC appear as intermediates of active DNA methylation during embryogenesis
In plants CpG, CpNpG and CpHpH methylation common
What processes is methylation involved in?
- embryonic development
- X chromosome inactivation
- Imprinting
- gene silencing
What is an example of epigenetic embryonic development?
Agouti gene mutation in mice
What does agouti encode for?
A paracrine signalling molecule that promotes follicular melanocytes to produce yellow pheomelanin rather than black eumelanin pigment. The mutant is a result of the insertion of a murine IAP transposable element ~100kb upstream of start site of the agouti gene
What happens if the diet is mice with agouti mutation are supplemented vs unsupplemented?
While pregnant both mothers fed Bisphenol A (BPA) but different diets:
- mothers of yellow mice received normal diet
- mothers of brown were supplemented with choline, folic acid, betaine and vitamin B12
What is X chromosome inactivation?
At ~1000 cell stage, cell choose one X chromosome to remain ON. Other is inactivated via XIST (X inactivation specific transcript) an X chromosome encoded LncRNA. XIST coats the X chromosome leading to heterochromatin spreading and methylation
What happens in mammalian X chromosome inactivation?
Early female embryo has both X’s active. Methylation patterns are heritable through mitosis, but reset during oogenesis. Fully developed female is a mosaic of different clones
What is genomic imprinting?
Parent-specific expression or repression of genes or chromosomes in offspring. Only the maternal or paternal allele is expressed.
Which allele is said to be imprinted in genomic imprinting?
The non-expressed allele
What is the evolutionary explanation for genomic imprinting?
The explanations remain controversial. The conflict/kinship theory posits that imprinting evolved as a result of different selection pressures on maternally and paternally derived selection pressures on maternally and paternally derived alleles
What are imprinted diseases characterized by?
By non-mendelian inheritance patterns that exhibit parental-origin effects. Symptoms suggest a role of imprinted genes in growth regulation during embryonic and postnatal development, brain function and behaviour
What are some examples of imprinted diseases?
- Beckwith-wiedemann syndrome
- prader-Willi syndrome
- angelman syndrome
- wilms tumour
- fragile X syndrome
- myotonic dystrophy
What 2 diseases both involving imprinting defects at 15q11-q13?
Angelman syndrome and Prader-Willi syndrome
What is Angelman syndrome?
Severe mental retardation, microcephaly, lack of speech, frequent laughter. Result of deletion of maternal 15q11-q13 (loss or inactivation of maternal UBE3A gene)
What is Prader-Willi syndrome?
Mild mental retardation, obesity, short stature. Result of deletion of paternal 15q11-q13 (loss or inactivation of maternal UBE3A gene)
