epigenetics Flashcards
describe epigenetics
1) change gene activity (transcription) without changing DNA sequence
- large stretches of DNA regulated by reversible, non-sequence specific alterations of DNA/ associated chr proteins (dna methylation + histone modification)
2) compared to DNA sequence, epigenetics is:
1- regulated
2- reversible
3) maintains level of gene activity even after DNA replcaition
- epigenetic marks are PASSED onto offspring
4) influenced by genetics, environment + developmental noise
describe structure of DNA (nucleosomes, histones, chromatin)
1 DNA organised in globular structures = nucleosomes
2 nucleosomes = made up of octamer of histones + ds DNA
3 : access to DNA depends on
1- histones
2- addition of chemical groups to DNA
3- heterochromatin
what factors can influence DNA methylation patterns
1) nutrients (vitamins)
- methyl donating nutrients
(folic acid-vit B9, vit B, Sam-e = key methyl making pathways)
- diet high in methyl donating nutrients = alter gene expression
2) environmental chemicals
3) drugs, pharmaceuticals
4) aging
what controls DNA accessibility
- chemical tags on DNA
2. histones
describe closed gene structure (heterochromatin)
- chromatin is condensed, inactive
- no transcription factors
- no transcription machinery
1) sequence specific recruiters bind to DNA
2) epigenome writers with enzymatic activity bind to DNA
3) epigenetic marks get writen
describe open gene structure (euchromatin)
- chromatin is loose, active
- gene transcription occurs
1) protein complexes read epigenetic marks (bc its open avaliable)
2) RNA polymerase able to bind –> initiates gene transcription + mRNA synthesis starts
what does acetylation + methylation do to HISTONES
- Acetylation = active chromatin
- methylation = depends on which amino acid is methylated (could be activating/inactivating)
what can enzymes do to epigenetic marks?
enzymes can ERASE epigenetic marks
describe DNA methylation
1) occurs to CpG island (where cytosine nucletodie next to guanine)
2) DNA methyltransferase (enzyme) add methyl groups to Cytosine of CpG island
3) changes structure of DNA = changes how the DNA interacts with transcription machinery
1-5% all C are methylated
how is DNA methylation passed onto offspring?
DNA methyltransferase recognise hemimethylated CpG site = 1 of the daughter strand CpG island is NOT methylated, so DNA methyltransferase will methylate the complementary CpG island
consequnece of highly methylated areas
- are more likely to be less transcriptionally active
- but it depends on the amino acid being methylated
diet impact on DNA methylation
- diet high in METHYL DONATING NUTRIENTS (folic acid, vit B, Sam-e) can change amount of DNA methylation = change gene expression
- especially important during early years where epigenetic markers are being estbalished
Queen Bee example
- both worker bee + queen bee are genetically identical as larvae
- larve that are destined to become queen bees are fed ROYAL JELLY
- ROYAL JELLY will:
1) silence Dnmt3 gene - Dnmt3 gene = usually codes for enzyme that silences group of Queen genes
- silence Dnmt3= silence enzyme that would usually silence queen genes = express queen gens
2) develop ovaries, larger abdomen (egg laying) + queen bee behaviour (rivarly w other queen bees)
Agouti mice example
- agouti protein = responsible for:
1- coat colour
2- body weight
mice that carry mutation to agouti protein = prone to being obese, yellow + ^ risk of cancer + diabetes
before, during + after pregnancy = diet rich in:
- folate acid
- Vit b12
- choline
- betaine
can cause epigenetic changes that convert phenotype back to Thin, Brown pups
- LEVEL OF METHYLATION IN BROWN MICE IS HIGHER THAN IN YELLOW + FAT MICE (BOTH ARE GENETICALLY IDENTICAL)
what does agouti mice example of epigenetic tell us
that diet before, during & after pregnancy is important = can have epigenetic effects
- diet rich in folic acid, vit b12, choline, betaine = all can change epigenetic events = revert mice back to thin, brown mice
our health is dtermined by what we eat but also what our parents ate
