Epigenetics Flashcards
Methylation
98% of genome at a time
Tells not to trx
Promoter region is less methylated then other regions 1cpg island/10bps vs 1 CpG for 100bps
CpG islands
TSS of housekeeping genes
Imprinting
Father/Mother give their methylated/unmethylated genes directly to child, then lose methylation until baby, then high methylation again
Imprinted genes expressed preferentially from one allele
-the expressed gene is not methylated
How to add/get rid of methyl
Methyl writers/erasers
DNMT/DMTase
Sometimes replicated cells are not methylated-use de novo DNMT addition
Methyl group functionality
Can have trx factors bind (function as promoter/inhibitor)
Rett Syndrome
X linked dominant, dev normally for 6-18 months, apraxia, breathing abnormalities
Results because missing methyl CpG binding protein MECP2-increase trx of genes that should be off
Boys die after birth because only 1 X chrome-more fatal
MECP2
inhibits trx, no binding to methylated CpG island, large amount in neurons
Methylation pattern
Similar when twins are born, very different as get older, each tissue of body has different amounts of methylation
Post translational Mod of Histones (4 types)
Covalent bonds, Reversibly modified Tell if chromatin relaxed or not Acetylation of lysine-relax Phosphorylation of serine Methylation of lysine-condense Sumoylation
HDAC
histidine deacytylases
used in cancer
small molecules that compact histones by removing acetylene
histone writers
methyltransferases and HATs/Kinases
histone erasers
HDACs and demethylases
Euchromatin histone mods
acetylation up, methylation down, H3-K4 is methylated
Heterochromatin histone mods
low acetylation, high methaltion, H3-K9 methylated
Bar bodies
Inactivated X chromasome, calico cat
X-inactivation Center
Both Xist and Tsix produce noncoding mRNA transcripts
Tsix antisense to Xist so can bind
Before inactivation Xist expressed at low concentrations in both chromosomes
Shortly after 1 chrom begins to express Tsix in high levels, inhibits Xist
This is active X chromosome
Chromosomes are really close together-kiss exchange factors and this results in 1 expressing more Tsix
Xist inactivation
Starts from one point, radiates outward, recruits histones H3 and H4 for hypoacetylation
Phenotypical plasticity
Can have multiple phenotypes with one genotype-arise from organism to respond to environment or as modification of developmental events (sustained neuronal activity, drugs, mood disorders)
Hongerwinter
No food, many diseases, small and short in stature kids, have problems that follow them throughout life
Hypomethylation in IGF2-gene that is maternally imprinted-kids of hongerwinter children (mothers only) had kids with same long term problems
IGF-2 gene
Maternally imprinted has differential methyl region-result in 1 gene have balletic expression
Agouti gene
Has variable methylated region
mRNA made during development and silenced rest of life
Unsilenced=yellow and diabetes problems
These mice are genetically identical
Follate (b6) and Choline (b12)
Methyl supplementors
Used in Ag mouse-no agouti symptoms
Ag gene methylated
Bisulfite Conversion
Bisulfite converts C to U if C is unmethylated
U can be in DNA-becomesT in when replicated
Methyl Sensitive enzymes
Useful for determining methylation pattern
Cancer to normal has different methylation pattern
