intro to epigenetics Flashcards
categories of epigenetic changes
DNA methylation
histone modification
miRNA
where does DNA methyl transferase add methyl groups
CpG islands (specific areas of DNA where CpG are concentrated)
CpG islands are located
in the promoter region and first exon of genes
methylation of CpG islands serves as a
switch that can silence downstream gene because mostly housekeeping genes are methylated
when DNA is methylated
it displaces transcription factors that normally bind to DNA
–attracts methyl-binding proteins, which in turn are associated with gene silencing, chromatin compaction
genes switched on by histone mod/dna methylation
active (euchromatin)
unmethylated cystoine
acetylated histones
genes switched off
silent (heterochromatin)
methylated cytosine
deacetylated histones
mRNA
small non-coding RNA that is 19-23 bp long, single stranded, and binds to compl mRNA
miRNA biogenesis
polymerase II or III make pri-miRNA
complex with RNAase III enzyme (Drosha) cleaves primiRNA–>premRNA
exportin 5 transports to cell cytoplasm
Dicer makes miRNA:miRNA*
goes on to make miRISC (miRNA associated RNA-induced silencing complex)
miRISC actions
interacts with target mRNA and exhibits its cellular effects, if perfect match mRNA cleaved and degraded, but if imperfect binding, translational repression
DNA methylation patterns can be
tissue specific heritable
genomic imprinting
inherit only one working copy either from mom or dad depending on gene–epigenetic tags stay for life except for gametogenesiss
genetic imprinting chromosome 115q11-q13
deletion of paternal chromosome= prader willi
deletion of maternal chromosome= angelman
prader-willi syndrome
mental retardation short stature hypotonia hyperphagia obesity small hands, feet, and gonads
angelman
mental retardation
ataxic gait seizures
inappropriate laughter
Fragile X syndrome
trinucleotide repeat disorder (CGG); x-linked
macro-orchidism, unique face structure, autism, mitral valve prolapse
fragile x genetics
repeats in 5’ UTR of FMR1 gene
normal: 6-31
premutation: 44-200
full mutation: >200
FMR1
regulatory protein important for binding mRNA particularly in neurodevelopment
hypermethylation = silencing
what is required for cancer?
initiation-genetic
promotion- non-genetic (usually epigenetic)
progression
spontaneous deamination
hydrolysis rxn where C–>U + NH3
- has a role in generation of some oncogenic point mutations
inactivation of tumor suppressor genes
meth serves to silence genes by making them inaccessible to TFs
p16
solid tumors
p15
acute leukemia
MGMT
DNA repair protein that removes mutagenic and cytotoxic adducts from OMGT
hypermethylation silences so fail to remove OGMT–> converstion of GC–>AT (mutations may be protooncogenes)
