Epigenetics Flashcards
What is chromatin?
Complex of DNA and proteins into which eukaryotic chromosomes are packaged
What is included in a nucleosome?
An octomeric histone core with 2 subunits of H2A, H2B, H3, and H4, with 147 base pairs of DNA
What are histones?
Positively charged DNA binding proteins with flexible tails
What is linker DNA?
DNA between histones
What do H1 histones do?
Linker histones that are involved in the assembly of nucleosomes into higher order structures
What are the two types of chromatin?
Euchromatin and heterochromatin
What is heterochromatin? Is it being transcribed?
Chromatin that is highly dense and compacted. It is not being transcribed
What is euchromatin? Is it being transcribed?
Chromatin that is more loosely packaged. Is being transcribed
Is chromatin always either euchromatin or heterochromatin?
No, it’s a lot more complicated and chromatin can quickly shift between the two
What are 3 common histone modifications?
Methylation, acetylation, and phosphorylation
What is histone acetylation?
Acetyl groups are added to lysine residues in the histone tails. They are rapidly reversible
What type of enzyme adds acetyl groups to histones?
Histone acetylases (HATs)
What type of enzyme removes acetyl groups from histones?
Histone deacetylases (HDACs)
Does histone acetylation typically activate or repress gene expression?
Activate
Does histone methylation typically activate or repress gene expression?
Can be either
What are 3 factors that determine whether histone methylation activates or represses gene expression?
- Which amino acids in the histone tail gets methylated
- Which gene
- Any other modifications
Is H3K9 methylation associated with activated or repressed gene expression?
Repressed
Is H4K4 methylation associated with activated or repressed gene expression?
Activated
What are writer enzymes?
Enzymes that add histone modifications
What are eraser enzymes?
Enzymes that remove histone modifications
What are reader enzymes?
Enzymes that recognize histone modifications
What are 3 mechanisms by which histone modifications change gene expression?
- Recruit nucleosome and chromatin remodelling proteins to change promoter accessibility
- Changing DNA accessibility
- Recruiting TFs
Are nucleosomes randomly distributed through the genome?
Nope
What is nucleosome positioning?
A measure of how often a nucleosome is in a particular spot at a particular time
What are 3 ways to describe nucleosome positioning?
Perfect, partial, or no positioning
What is perfect nucleosome positioning?
The nucleosome is always in the same spot in every cell of a certain type under certain conditions
What is partial nucleosome positioning?
The nucleosome is often, but not always in the same spot in every cell of a certain type under certain conditions
What is no nucleosome positioning?
Random
What regions of the genome tend to be nucleosome poor?
Where things bind. Promoters, enhancers, terminators
Where would perfect positioning be found?
Next to nucleosome poor regions
What is nucleosome occupancy?
How frequently a locus tends to be occupied by nucleosomes, and how many
How much genomic DNA is occupied by nucleosomes?
Most of it
What sorts of regions have low nucleosome occupancy?
Functional regions
What is a poised/closed enhancer?
The histones have a modification that allows for the enhancer to be accessible, but also another one that prevents that. The enhancer becomes available for binding once the repressing modification is removed
What is a latent enhancer?
When the histones need a certain modification to become accessible, and do so once they receive that modification
What do antirepressor transcription factors do?
Have the ability to overcome the repressive effects of chromatin and activate transcription, even when the chromatin is in a repressive state
What are 5 factors that influence nucleosome positioning?
- DNA sequence. A and T rich sequences aren’t bound by nucleosomes as much
- Histone modifications
- Nucleosome remodelling enzymes
- RNAP II and GTFs
- TFs
Why is competent chromatin structure necessary, but not sufficient for transcription to occur?
Still need RNAP II and the GTFs. But chromatin has to be competent for them to bind in the place