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Developmental Genetics and Embryonal Cancers > Epigenetic Regulation of Gene Expression > Flashcards

Epigenetic Regulation of Gene Expression Flashcards

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Biology 101 flashcards
1
Q

Where is DNA methylated

A

on the 5 position of cytosine

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2
Q

What is the enzyme and donor for DNA methylation

A

DNMT - enzyme

SAM - donor

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3
Q

What are the requirement of a CpG island

A

over 60% G+C content
CpG:GpC >0,6 ration
>200bp

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4
Q

What are the 2 methods of demethylation

A

TET genes

Active process using TDG

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5
Q

How do TET genes demethylate DNA

A

modifies methylcysteine to hydroxymethylcytosine –> this a poor substrate for DNMT1 and methylation is lost upon cell divison

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6
Q

How does repair mediated processes demethylate DNA

A

Use the TDG enzyme which removes a base in base-excision repair

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7
Q

What is the DNMT for maintenace

A

DNMT1

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8
Q

What are the de novo DNMTs

A

DNMTs3a/3b

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9
Q

What are the effects of knockouts of each DNMT

A

DNMT1 % 3a/b –> embyronically lethal

DNMTL –> involved in genomic imprinting hence get biallelic expression from normally parentalyl imprinted genes

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10
Q

How does DNA methylation cause a repressive chromatin structure

A

Methylated DNA binds MBP and rectuirs HACs

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11
Q

What is the state of CTCF in maternal chromomsomes

A

Locus is not methylated hence CTCF can bind and therefore igf2 does not have access to the enhance

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12
Q

What are the active histone methylations

A

H3K4

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13
Q

What are the repressive histone methylations

A

H3K9 , H3K27

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14
Q

How doe histone methylations recurit DNMt

A

HP-1 proteins can attract DNMTs

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15
Q

Name some biological functions of epigenetically silencing genes

A

X-inactivation
Inativation of parasitic sequences
Genomic imprinting

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16
Q

what are the parental origins of a mule and hinney

A

Mule - male donkey, female horse

Hinney - male horse, female donkey

17
Q

what do yo uget if you get LOI and LOH at the 11p15 locus in somatic cells

A

Wilms Tumour

18
Q

what do yo uget if you get LOI and LOH at the 11p15 locus in germline cells

A

Overgrowth BWS

19
Q

What occurs if you get H19 DMR hypomethylation –> meaning that h19 is overexpressed

A

Russel silver syndrome

growth retardation

20
Q

What are the 2 theories of imprinting

A

Haig

Barlow –<> methylation is a defence against foreign DNa

21
Q

What specific histone methyltransferase inactivaates oct4

A

G9a –> induces H3K9me2 and recruits DNMT hence inactivating Oct4 allowing for differentiation

22
Q

Deletion in prada willi syndorme

A

15q11 deletion –> loss of paternal expression of genes –> mainly due to paternal deletion

23
Q

What are the symptoms of prada-willi syndrome

A

Poor suckling, hyperphagia, obesity, developmental delay

24
Q

What are the symptoms of BWS

A 
Big body: macrosomia
Big tonigue: macroglossia
Big abdomen: Omphacele
Big organs: visceromegaly
Getting bigger: can get tumorus e.g. Wilms and NB
25
Q

How many clusters of imprinted genes have we identified so far

A

13

26
Q

Describe a gene that doesnt show predominant expression from a maternal or paternal allel

A

Grb10
Maternally expressed in embryogenesis
However paternally expressed in adults and can regulate social behaviour

27
Q

Descrbie the 2 methods throguh whcih ICR work

A

LncRNAs

Insulator model

28
Q

What is the link between imprinting and adiposity

A

Gnas mutations –> can lead to severe obseity not due to hyperphagia

29
Q

Mutation of what imprinted gene can affect neonatal feeding

A

Loss of Magel2 imprinted gene (normally paternally expressed)
Interestingly also get low oxytocin in the hypothalamus –> potential to give an oxytocin shot at birth to correct this

30
Q

Defects in imprinting genes can affect sleep in what conditions

A

Angelmanns

Prade Willi

31
Q

What are the 2 theories of imprinting

A

Haig

Barlow

32
Q

WHere does less CpG depletion occur

A

At CpG islands –> may be because these remain unmethylated in the germ line

33
Q

What can increases the activtiy of TET genes

A

Vitamin C

34
Q

What domain containing proteins can recogenise methylated CGs and may contributed to methylated mediated repression

A

MBD-containing proteins

Although may be redundant as deletion does not lead to reactivation of genes

35
Q

What domain containing proteins can recorgnise unmethylated CpGs

A

CXXC

36
Q

TET2 mutations are linked to what disease

A

TET2

37
Q

What is a commonly mutated gene releated to methylation in AML

A

DNMT3a –> one of the most commonly mutated genes in AML

Developmental Genetics and Embryonal Cancers (18 decks)

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