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Path3 > intro to epigenetics > Flashcards

intro to epigenetics Flashcards

1
Q

categories of epigenetic changes

A

DNA methylation
histone modification
miRNA

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2
Q

where does DNA methyl transferase add methyl groups

A

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

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3
Q

CpG islands are located

A

in the promoter region and first exon of genes

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4
Q

methylation of CpG islands serves as a

A

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

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5
Q

when DNA is methylated

A

it displaces transcription factors that normally bind to DNA

–attracts methyl-binding proteins, which in turn are associated with gene silencing, chromatin compaction

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6
Q

genes switched on by histone mod/dna methylation

A

active (euchromatin)
unmethylated cystoine
acetylated histones

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7
Q

genes switched off

A

silent (heterochromatin)
methylated cytosine
deacetylated histones

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8
Q

mRNA

A

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

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9
Q

miRNA biogenesis

A

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)

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10
Q

miRISC actions

A

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

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11
Q

DNA methylation patterns can be

A

tissue specific heritable

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12
Q

genomic imprinting

A

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

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13
Q

genetic imprinting chromosome 115q11-q13

A

deletion of paternal chromosome= prader willi

deletion of maternal chromosome= angelman

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14
Q

prader-willi syndrome

A 
mental retardation
short stature
hypotonia
hyperphagia
obesity
small hands, feet, and gonads
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15
Q

angelman

A

mental retardation
ataxic gait seizures
inappropriate laughter

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16
Q

Fragile X syndrome

A

trinucleotide repeat disorder (CGG); x-linked

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

17
Q

fragile x genetics

A

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

18
Q

FMR1

A

regulatory protein important for binding mRNA particularly in neurodevelopment

hypermethylation = silencing

19
Q

what is required for cancer?

A

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

20
Q

spontaneous deamination

A

hydrolysis rxn where C–>U + NH3

- has a role in generation of some oncogenic point mutations

21
Q

inactivation of tumor suppressor genes

A

meth serves to silence genes by making them inaccessible to TFs

22
Q

p16

A

solid tumors

23
Q

p15

A

acute leukemia

24
Q

MGMT

A

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
Q

why could hypermeth of MGMT be good

A

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

26
Q

MGMT methylation in colorectal cancer

A

does NOT confer sensitivity if tumor is also mismatch repair deficient

27
Q

how is MMR system inactivated

A

germline mutations in MMR genes-MLH1, MSH2

hypermethylation of promoter- silences transcription of MLH1

28
Q

HNPCC inactivation

A

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

–>microsatellite instability and dev of tumors

29
Q

sporadic CRC

A

methylation of both alleles of promoter of MLH1

30
Q

three subtypes of rena cell carcinoma

A

clear cell
papillary
chromophobe

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

31
Q

hypoxic pathway

A

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

32
Q

majority of methods for methylation analysis consist of

A

converting unmethylated cytosine to uracil by Na bisulfite (deaminates)

5-methycystosine is resistant to this

Path3 (11 decks)

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