Epigenetics - Nelson Flashcards
4 categories of epigenetic DNA modification
DNA methylation
Histone modifications by methylation, acetylation, and phosphorylation
DNA reprogramming
Gene regulation by small, double-stranded RNAs
Generally, what does DNA methylation do?
Turns genes off
Maintenance DNA methyltransferase
Enzyme that will act to match the methylation of a copy strand from its original methylated strand of DNA
What happens if DNA methyltransferase is over expressed?
Too much DNA methylation can occur and the gene will be undesirably silenced. Prevalent in cancer
de novo DNA methyltransferase
Enzyme that methylates new cytosines. Occurs much in embryology
It also works in conjunction with maintenance DNA methyltransferase to methylate DNA. (ex. knockout of DNMT3A alone, reduced methylation only 3%…knockout of DNMT1+DNMT3A = 95% reduced methylation, so gene stays on in colorectal cancer)
What nucleotide is usually methylated?
Cytosine
How can histones be modified?
Methylation/de, phosphorylation/de, acetylation/de
What do histone modifications do?
Affect the binding of DNA to other histones and proteins to other chromatin
What is bisulfite sequencing used for?
Method used to determine 5 methyl cytosine (5mC) bases in DNA. Can ultimately sequence entire epigenome
What are two methods of gene silencing by RNA?
RNA-mediated destruction of mRNAs in the cytoplasm or RNA interference (RNAi)
RNA directed DNA methylation (RdDM)
RISC
RNA induced silencing complex
Argonaute protein
Main protein component of the RISC. Slices the siRNA after dicer extracts it from dsRNA and slices it. Passenger strand is cleaved
Dicer
Takes miRNA strand from long dsRNA