Epigenetics, Imprinting and Genetics of Ageing Flashcards
How is cell identity defined?
By a unique transcriptional programme which is locked into place by epigenetic modification
What is epigenetics?
The study of modification that alter phenotype without altering the genotype
How can histone tails be modified?
Phosphorylation
Acetylation
Methylation
Ubiquitination
What bases does DNA methylation occur?
Adenine - Prokaryotes
Cytosine - Eukaryotes
In eukaryotes, what place does methylation occur?
At CpG dinucleotides
What is the principal role of DNA methylation?
Switch off transcription long term
What are the properties of DNA methyltransferase 1 (Dnmt 1)?
Replication dependent
Maintenance
What are the properties of DNA methyltransferase 3a/3b (Dnmt 3a/3b)?
De novo
What does DNA methyltransferase silence?
Retrotransposons Endogenous retroviruses and trasnposons Repetitive sequences (e.g. centromeres)
How does DNA methylation lead to a long-term silencing?
Proteins bind to methylated cytosine
Interaction prevents expression of the gene
How is ChIP-seq done?
Cross link proteins onto DNA, shear into small molecules, use antibodies against protein of interest, digest DNA, seq protein
What is the biggest obstacle to reprogramming a cell?
The epigenetic modification - difficult to make a differentiated cell lose its methylation status
Mammalian cell do not do DNA demethylation
What is genomic imprinting?
Differential marking of parental alleles of specific genes or chromosome regions during gametogenesis leading to differential expression during development
What are the features of an imprinted gene?
Epigenetic modifications of DNA or chromatin
Paternal origin of each allele is distinguished
Only one allele is expressed
Imprint must be stable and heritable
Imprint must be reversible in germline
What is ageing?
Intrinsic deterioration process - leads to impairment of function, increasing vulnerability to environmental challenge, an increase likelihood of death and a decline in fertility