Epigenetics

Question 1

epigenetics

definition

Answer 1

study of changes in gene expression that do not result from changes in DNA sequence

via silencing or activating chromosomal regions

Question 2

chromatin remodelling/histone rearranging

Answer 2

SWI/SNF = facilitate transcription by repositioning/swiping histones to expose for DBP

ISWI/CHD= inhibit transcription by loading histone on DNA to occlude binding sites

DNA binding proteins

Question 3

DNA methylation

Answer 3

@cytosines in CG sequences

does NOT affect base pairing

DOES affect methylation-sensitive DNA binding proteins aka prevent transcriptional activators or promote chromatin silencing factors (histones)

Question 4

methylated regions in genome

Answer 4

either @repetitive DNA or @promoter regions (CpG islands)

-unmethylated in transcribed regions, methylated in silent

Question 5

hypermethylation

Answer 5

will silence important genes like tumor suppressors

Question 6

hypomethylation

Answer 6

can activate wrong genes like oncogenes

causes genome instability with retrotransposons bc can make copies of itself and insert into DNA

Question 7

methylation

establishment and maintenance

Answer 7

established: by writing on unmethylated DNA by DNMT3
-initially on one strand

maintenance and copying: by DNMT1
-copied on second strand

after DNA replication only hemi-methylated again so copied/maintained again

Question 8

erasing methylation

Answer 8

active demethylation by TET enzymes then base excision

passive demethylation by inhibiting DNMT1 so after DNA replication no maintenance

Question 9

TET mutations

Answer 9

inc tumor risk

TET requires alpha-ketoglutarate from TCA

Question 10

histone modifications

acteylation

Answer 10

actetylation of lysine residues in histone tail dec affinity to DNA so opens chromatin and facilitates transcription

activation = activates

Question 11

histone modifications

methylation

Answer 11

@lysine residues

facilitates binding of regulatory proteins
-activating by H3K4met
-repressing by H5K9met

Question 12

histone modifications

other

Answer 12

phosphorylation
ubiquitination

Question 13

writing histone codes

Answer 13

by HATs (acetyl)
activate transcription

or HMTs (methyl)
different reg functions

Question 14

readers of histone code

Answer 14

methylation sensitive histone binding proteins i.e HP1

activate chromatin modifying enzymes

Question 15

erasers of histone code

Answer 15

HDACs

repress transcription

Question 16

metabolism and epigenetics

Answer 16

metabolism gives substrates for chromatin modification
1. acetyl CoA for histone acetylation and NAD+ as cofactor
2. SAM for DNA and histone methylation and alpha-ketoglutarate as cofactor for demethyl

Question 17

boundary elements

Answer 17

separate heterochromatin from euchromatin i.e HP1

translocation of methylated fragments = silence adj regions

if elements fail > inactivation of adj regions so behaves like a mutation

Question 18

Rett Syndrome

Answer 18

mutation in methyl-cytosine bindng protein MECP2 gene = lose transcriptional silencing

onset 6-18 mo, autism like, repetitive teeth grinding, hand wringing, motor probs, gait,
-will stabilize after inital deterioration

X linked dominant- affected boys die shortly after birth

Question 19

imprinting

Answer 19

parent of origin monoallelic expression aka alleles are silenced/imprinted on either mom or dad

explains why phenotype of a mutation varies depending on which parent, and why zygotess with DNA from just one parent are inviable

Question 20

monoallelic expression

Answer 20

impacts a few genes- can be dependent on parent of origin or random

most genes- bi-allelic expression

Question 21

parent of origin effect

Answer 21

genes with poo specific imprint normally = balanced amount of protein
-uniparental disomy upsets monoallelic balance

if deletion on pat/maternal homolog abolishes expression of different genes

Question 22

Prader Willi syndrome

Answer 22

deletion on paternal copy of chromo 15 or maternal uniparently disomy

overgrowth, xs food seeking

Question 23

angelman syndrome

Answer 23

deletion on maternal copy of chromo 15

autism like features

assoc w/ UBE3A ubiquitin protein ligase

Question 24

Beckwith-Wiedemann Syndrome

Answer 24

paternal uniparental disomy of chromo 11

overexpress IGF2 = organ problems

microcephaly, macroglossia, umbilical hernia

Question 25

hypomethylation

cancer

Answer 25

causes instability =
elevated transposon activity
chromo abnormalities
high mutation rate