Epigenetics III: Imprinting

Question 1

Imprinted genes are expressed ____________, in a parental-origin-specific manner

Answer 1

Monoallelically

Question 2

What experiment was done to provide early evidence for imprinting in mammals?

Answer 2

Mouse embryos constructed by pronuclear transfer

Question 3

What were the results of the pronuclear transfer experiment?

Answer 3

Male and female pronuclei gave rise to normal, viable embryo
Only male pronuclei or only female pronuclei gave rise to abnormal, not viable embryo

Question 4

What can be done to restore the viability of the embryo?

Answer 4

Turning on both maternally or paternally silenced genes

Question 5

Where are imprinted genes typically found?

Answer 5

In large clusters

Question 6

What controls imprinted gene clusters?

Answer 6

Imprinting control region (ICR)

Question 7

What is the consequence of deleting the ICR on the paternal allele?

Answer 7

Disruption of the expression pattern for the entire cluster

Question 8

In which embryonic stage are there high levels of expression of imprinted genes?

Answer 8

Prenatal stage

Question 9

What are the functions of imprinted genes?

Answer 9

Growth and metabolism, neurological development, development of the placenta

Question 10

True or false: Imprinting is disrupted in cancer cells

Answer 10

True

Question 11

Which hypothesis states that imprinted genes reflect competition between males for limited female resources?

Answer 11

Parental conflict hypothesis

Question 12

If a single female mates with multiple males, what are the intentions of the males and females for their offspring?

Answer 12

Males want to ensure that their offspring outcompete the others
Females want to ensure that all their offspring receive resources

Question 13

ICRs are CpG islands that are differentially methylated between the __________ allele and _________ allele

Answer 13

Paternal; maternal

Question 14

Which DNA methyltransferases establish imprinting genes?

Answer 14

DNMT3A in the germline and DNMT1 for maintenance

Question 15

When do imprinted genes get erased?

Answer 15

During germ cell migration to the developing gonads

Question 16

What are the two stages in which DNA methylation is removed?

Answer 16

Early embryo and germ cell development

Question 17

Imprinting establishment occurs during germ cell development after ____________ erasure of DNA methylation

Answer 17

Genome-wide

Question 18

What are the two types of imprinting mechanisms involving DNA methylation?

Answer 18

Maternally methylated DMRs and ICRs are located at promoters and block promoter function
Paternally methylated DMRs and ICRs are located between genes and affect enhancer function

Question 19

Igf2 is expressed from the (paternal/maternal) allele, while H19 is expressed from the (paternal/maternal) allele

Answer 19

Paternal; maternal

Question 20

When do Igf2 knockouts have reduced size at birth?

Answer 20

If they get the knockout allele from the father

Question 21

The ICR region between heterologous ____________ and promoter that prevent ___________ activity is called an insulator

Answer 21

Enhancer

Question 22

What is the mechanism of the methylation of ICR with the binding of CTCF?

Answer 22

When ICR is unmethylated, CTCF can bind to insulator and H19 is expressed; Igf2 is blocked (maternally)
Methylation of ICR blocks CTCF binding to insulator and Igf2 is expressed; H19 is blocked (paternally)

Question 23

Maternal-specific methylation typically silences __________ of long non-coding RNAs located __________ protein-conding genes

Answer 23

Promoters; inside

Question 24

IncRNA is transcribed (sense/antisense) to Igf2r and Kcnq1

Answer 24

Antisense

Question 25

How does IncRNA transcription lead to silencing within the imprinted domain?

Answer 25

Antisense transcription interferes with sense transcription
The RNA itself recruits chromatin modification enzymes to silence transcription

Question 26

Associate the following to either oocyte DNAme pattern or sperm DNAme pattern
a. Present in most/all gene bodies
b. Present in intergenic regions
c. Specific enrichment in the bodies of genes transcribed

Answer 26

a. Sperm
b. Sperm
c. Oocyte

Question 27

How is imprinted methylation maintained?

Answer 27

Factors that bind to ICRs and H3K9 methylation

Question 28

How does Zfp57 contribute to imprinting maintenance?

Answer 28

Binds to methylated sequence at ICRs and recruits H3K9 methyltransferase SETDB1

Question 29

Which syndromes are caused by deletion of the entire imprinted domain on chromosome 15?

Answer 29

Prader-Willi and Angelman syndromes

Question 30

AS is caused by (paternal/maternal) transmission of the deletion and PWS is caused by (paternal/maternal) transmission

Answer 30

Maternal; paternal

Question 31

What causes Beckwith-Wiedemann Syndrome?

Answer 31

Loss of imprinting at KNCQ1 and IGF2 loci