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Flashcards in intro to epigenetics Deck (32):
1

categories of epigenetic changes

DNA methylation
histone modification
miRNA

2

where does DNA methyl transferase add methyl groups

CpG islands (specific areas of DNA where CpG are concentrated)

3

CpG islands are located

in the promoter region and first exon of genes

4

methylation of CpG islands serves as a

switch that can silence downstream gene because mostly housekeeping genes are methylated

5

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

6

genes switched on by histone mod/dna methylation

active (euchromatin)
unmethylated cystoine
acetylated histones

7

genes switched off

silent (heterochromatin)
methylated cytosine
deacetylated histones

8

mRNA

small non-coding RNA that is 19-23 bp long, single stranded, and binds to compl mRNA

9

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)

10

miRISC actions

interacts with target mRNA and exhibits its cellular effects, if perfect match mRNA cleaved and degraded, but if imperfect binding, translational repression

11

DNA methylation patterns can be

tissue specific heritable

12

genomic imprinting

inherit only one working copy either from mom or dad depending on gene--epigenetic tags stay for life except for gametogenesiss

13

genetic imprinting chromosome 115q11-q13

deletion of paternal chromosome= prader willi
deletion of maternal chromosome= angelman

14

prader-willi syndrome

mental retardation
short stature
hypotonia
hyperphagia
obesity
small hands, feet, and gonads

15

angelman

mental retardation
ataxic gait seizures
inappropriate laughter

16

Fragile X syndrome

trinucleotide repeat disorder (CGG); x-linked

macro-orchidism, unique face structure, autism, mitral valve prolapse

17

fragile x genetics

repeats in 5' UTR of FMR1 gene
normal: 6-31
premutation: 44-200
full mutation: >200

18

FMR1

regulatory protein important for binding mRNA particularly in neurodevelopment

hypermethylation = silencing

19

what is required for cancer?

initiation-genetic
promotion- non-genetic (usually epigenetic)
progression

20

spontaneous deamination

hydrolysis rxn where C-->U + NH3
- has a role in generation of some oncogenic point mutations

21

inactivation of tumor suppressor genes

meth serves to silence genes by making them inaccessible to TFs

22

p16

solid tumors

23

p15

acute leukemia

24

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)

25

why could hypermeth of MGMT be good

inactivation leads to sensitivity to alkylating agents-->better rxn to chemo-->better survival and overall prognosis

26

MGMT methylation in colorectal cancer

does NOT confer sensitivity if tumor is also mismatch repair deficient

27

how is MMR system inactivated

germline mutations in MMR genes-MLH1, MSH2

hypermethylation of promoter- silences transcription of MLH1

28

HNPCC inactivation

1 allele inactivated by germline mut, another inactivated by hyper meth

-->microsatellite instability and dev of tumors

29

sporadic CRC

methylation of both alleles of promoter of MLH1

30

three subtypes of rena cell carcinoma

clear cell
papillary
chromophobe

can be distinguished by miRNA profile because they upreg/downreg different ones

31

hypoxic pathway

HIF1 (regulated by VHL) upregulates mir210 so that it can downregulate some specific genes

32

majority of methods for methylation analysis consist of

converting unmethylated cytosine to uracil by Na bisulfite (deaminates)

5-methycystosine is resistant to this