Epigenetic Regulation of Gene Expression Flashcards
Where is DNA methylated
on the 5 position of cytosine
What is the enzyme and donor for DNA methylation
DNMT - enzyme
SAM - donor
What are the requirement of a CpG island
over 60% G+C content
CpG:GpC >0,6 ration
>200bp
What are the 2 methods of demethylation
TET genes
Active process using TDG
How do TET genes demethylate DNA
modifies methylcysteine to hydroxymethylcytosine –> this a poor substrate for DNMT1 and methylation is lost upon cell divison
How does repair mediated processes demethylate DNA
Use the TDG enzyme which removes a base in base-excision repair
What is the DNMT for maintenace
DNMT1
What are the de novo DNMTs
DNMTs3a/3b
What are the effects of knockouts of each DNMT
DNMT1 % 3a/b –> embyronically lethal
DNMTL –> involved in genomic imprinting hence get biallelic expression from normally parentalyl imprinted genes
How does DNA methylation cause a repressive chromatin structure
Methylated DNA binds MBP and rectuirs HACs
What is the state of CTCF in maternal chromomsomes
Locus is not methylated hence CTCF can bind and therefore igf2 does not have access to the enhance
What are the active histone methylations
H3K4
What are the repressive histone methylations
H3K9 , H3K27
How doe histone methylations recurit DNMt
HP-1 proteins can attract DNMTs
Name some biological functions of epigenetically silencing genes
X-inactivation
Inativation of parasitic sequences
Genomic imprinting
what are the parental origins of a mule and hinney
Mule - male donkey, female horse
Hinney - male horse, female donkey
what do yo uget if you get LOI and LOH at the 11p15 locus in somatic cells
Wilms Tumour
what do yo uget if you get LOI and LOH at the 11p15 locus in germline cells
Overgrowth BWS
What occurs if you get H19 DMR hypomethylation –> meaning that h19 is overexpressed
Russel silver syndrome
growth retardation
What are the 2 theories of imprinting
Haig
Barlow –<> methylation is a defence against foreign DNa
What specific histone methyltransferase inactivaates oct4
G9a –> induces H3K9me2 and recruits DNMT hence inactivating Oct4 allowing for differentiation
Deletion in prada willi syndorme
15q11 deletion –> loss of paternal expression of genes –> mainly due to paternal deletion
What are the symptoms of prada-willi syndrome
Poor suckling, hyperphagia, obesity, developmental delay
What are the symptoms of BWS
Big body: macrosomia Big tonigue: macroglossia Big abdomen: Omphacele Big organs: visceromegaly Getting bigger: can get tumorus e.g. Wilms and NB
How many clusters of imprinted genes have we identified so far
13
Describe a gene that doesnt show predominant expression from a maternal or paternal allel
Grb10
Maternally expressed in embryogenesis
However paternally expressed in adults and can regulate social behaviour
Descrbie the 2 methods throguh whcih ICR work
LncRNAs
Insulator model
What is the link between imprinting and adiposity
Gnas mutations –> can lead to severe obseity not due to hyperphagia
Mutation of what imprinted gene can affect neonatal feeding
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
Defects in imprinting genes can affect sleep in what conditions
Angelmanns
Prade Willi
What are the 2 theories of imprinting
Haig
Barlow
WHere does less CpG depletion occur
At CpG islands –> may be because these remain unmethylated in the germ line
What can increases the activtiy of TET genes
Vitamin C
What domain containing proteins can recogenise methylated CGs and may contributed to methylated mediated repression
MBD-containing proteins
Although may be redundant as deletion does not lead to reactivation of genes
What domain containing proteins can recorgnise unmethylated CpGs
CXXC
TET2 mutations are linked to what disease
TET2
What is a commonly mutated gene releated to methylation in AML
DNMT3a –> one of the most commonly mutated genes in AML
