L10 - epigenetics Flashcards
what is the key to complexity of living organisms
complex regualtion
what is epigenetics
regulation of gene expression independent of the dna sequence
is heritable
what levle does epigenetics occur at
gene level - silence promoter by methylation etc
domain level - cluster of imprinted genes
chr level - heterochromatin
what are some mechanisms of epigeneticcs
methulation
histone modification
non-coding rna
describe the mol detail of methylation
conversion of cytosine to 5 methyl cytonsine
this is not stable mol
easaily chnage to thymidine
why most mut are c to t chnage
where is methykation most likely to occur on dna
cpG island
short region of dna with high proportion og CG comp to rest of genome
give eg of type of histone modification and the markers
acetylation - H3K9ac
phosphorylation -H3S10P
methylation - H3K9me
what does histone modification do
defines strucutre
what are non coding rna
functional rna that do not code pr
inc miRNA/ siRNA snoRNA
all interact
how is miRNA processed and action
pre mi RNA processed by DROSA into hairpin
DICER complex tranforms into mature miRNA
RISC complex guides to dna
where can silence genes by binding to promoters etc
what is imprinting
gene expr depenent on parent of origin
how many genes in mammals found to show genomic imprinting
roughly 80
descirbe the mosue experiment that shown genomic imprinting occurs
parthenogenic embryo (2x mat genome) - ovarian teratoma / disorg fetus/ no mbns androgenic embryo (2x pat) vigorously grown mbn no embryo
- ev that some gene only from one parent
what central mech of genomic imprinting
methylation
what is used to detect methylation of seq
sodium bisuldate
converts c to u
then amplify and seq
can detect if methy if c - methy if t - not mehty
what parent of orgin is igf2 expr for
pat
if null = smaller
how is igf2-h19 cluster diff in the parent of origin
in the paternal allele h19 is methy at the IC promoter region = therefore igf2 expr as CTCF cant bind
in the mat CTCF binds to IC where insulates and no Igf2 expr
what diseases are assoc with the igf2-h19 locus
wilms tumour - failure of imprinting
beckwith-wiedemann syndrome - del of ic-biallelic expr of igf2
what diseases linked to the deletion of proximal portion of chr 15 (15q11) a cluster with mutliple imprint genes
angelamann syndrome
prader willi syndrome
what uniparentla disomy cause as and pws
2x mat - pws
2xpat - as
what the clinical features of as and pws
as - slow dev/unusal movememtn/happy puppet
pws - ahort/obesity/immature phy dev
how does uniparentla disomy occur
is the x2 chr from one parent
error in m2 disjucntion result in trisomy
then trisomy rescue remove extra chr and left with uniparental disomy
what occurs to imprint when passed on to next gen
erase and restablished new parent sex specific impring in gamete/zygote
why is x inact imp
compensate for gene dosage of male and female
when does x inact occur
random at 15-16 days
what does x inact lead to
mosaicism for functions coded bby heterosyg x link gene
eg calico cat
what controls the choice of x for inact and initiates
xic (x inact centre)
what is xist
x inact specific transcript element of xic initiates and propgates x inact coats the x chr for inact no xist - no inact
what is tsix
antisense xist
what does x inact require
descirbe process
2x xic
xic changes xist rna form unstabel to highly expr
xist pot recruit factors to help make heterochromatin
tsix speculated role in x inact as at onset of x inact become monoallele expr is assoc with the active x until xist turned off
what disease results from unbalandced x inact
duchene muscular dystrophy
fragile x
xaemophilia A
what disease result of numerical x chr abn
klinefelter
turner
