Epigenetics Flashcards
Define epigenetics
Anything other than DNA used to control inheritance of genetic information.
Name four modes of genetic inheritance through epigenetics
- DNA methylation
- modification of histone proteins
- non-coding RNAs
- chromatin remodelling
At what location is DNA methylated?
At CpG
When are DNA methylation patterns established?
During embryo development, and are maintained by copying mechanisms during cell replication
Describe the writers of DNA methylation.
DNA methyltransferases: dnmt3a and dnmt3b perform de novo methylation, and dnmt1 performs maintenance methylation
What are CpG islands?
Short stretches of DNA in which the frequency of CpG methylation is higher.
Describe DNA hypo- and hypermethylation.
Hypomethylation: less methylation, more expression.
Hypermethylation: more methylation, less expression (txn factors cannot bind)
Define and describe the readers of DNA methylation.
These proteins have a conserved methyl-binding domain as well as a variable transcriptional repression domain.
What is MeCP2?
It regulates transcription as a reader of DNA methylation. Depending on the types of proteins that bind to it, it can both activate and supress gene expression in neurodevelopment.
What is Rett Syndrome?
It is a disorder caused by mutations in MeCP2 methylation reader. It is an X-linked neurodevelopment disorder.
Describe DNA methylation erasers.
They are involved in passive or active DNA demethylation and include the TET (ten-eleven translocation) family enzymes.
What is active DNA demethylation?
It involved three different enzymes to carry out DNA repair:
- methylcytosine is hydroxylated by TET to form hydroxymethylated cytosine
- methylcytosine is deaminated by AID to form methyluracil
- these intermediates can be replaced with cytosine by BER
What are three roles for DNA methylation?
- gene silencing
- X-chromosome inactivation and genomic imprinting
- environmental factors induce epigenetic changes, leading to cancer
How does DNA methylation lead to cancer?
- Hypomethylation results in genome instability
- hypermethylation can silence tumor suppressor genes
- methylation sites are hotspots for C->T transitions
- methylation increases binding of chemical carcinogens and increase UV-induced mutations
How does methylation occur?
S-adenosyl methionine is formed by methionine and ATP and adds a methyl group to 5’ carbon of cytosine with the help of DNMTs.
What is the source of methyl groups for DNA methylation?
- flavenoids and soft fruits and soya inhibit DNMT and could help reverse hypermethylation to tumor suppressor genes!
- folates regulate methylation
- diet during early development can cause lasting changes into adulthood.
How does BPA affect DNA methylation?
Mice fed BPA had unhealthy babies, but when supplemented with folate rich foods, the babies were born healthy.
How do father’s diets affect DNA methylation and epigenetics?
Food availability to paternal grandfathers at a young age affects the lifespan of his children.
Shortage of food = longer lifespan. More food = shorter lifespan and death by cardiovascular disease or diabetes.
Nutritional info about environment captured and passed onto next generations!
Describe the drastic role of DNA methylation in honeybees.
- Queen been larvae feed on rolly jelly secreted by worker bees
- queens are fertile and behave differently, while workers are sterile (over 550 genes affected)
- both castes have same genome
- a DNMT3 denovo patterning on larvae in a jelly-like manner caused them to develop into queens