Epigenetics III: Imprinting Flashcards
Imprinted genes are expressed ____________, in a parental-origin-specific manner
Monoallelically
What experiment was done to provide early evidence for imprinting in mammals?
Mouse embryos constructed by pronuclear transfer
What were the results of the pronuclear transfer experiment?
Male and female pronuclei gave rise to normal, viable embryo
Only male pronuclei or only female pronuclei gave rise to abnormal, not viable embryo
What can be done to restore the viability of the embryo?
Turning on both maternally or paternally silenced genes
Where are imprinted genes typically found?
In large clusters
What controls imprinted gene clusters?
Imprinting control region (ICR)
What is the consequence of deleting the ICR on the paternal allele?
Disruption of the expression pattern for the entire cluster
In which embryonic stage are there high levels of expression of imprinted genes?
Prenatal stage
What are the functions of imprinted genes?
Growth and metabolism, neurological development, development of the placenta
True or false: Imprinting is disrupted in cancer cells
True
Which hypothesis states that imprinted genes reflect competition between males for limited female resources?
Parental conflict hypothesis
If a single female mates with multiple males, what are the intentions of the males and females for their offspring?
Males want to ensure that their offspring outcompete the others
Females want to ensure that all their offspring receive resources
ICRs are CpG islands that are differentially methylated between the __________ allele and _________ allele
Paternal; maternal
Which DNA methyltransferases establish imprinting genes?
DNMT3A in the germline and DNMT1 for maintenance
When do imprinted genes get erased?
During germ cell migration to the developing gonads
What are the two stages in which DNA methylation is removed?
Early embryo and germ cell development
Imprinting establishment occurs during germ cell development after ____________ erasure of DNA methylation
Genome-wide
What are the two types of imprinting mechanisms involving DNA methylation?
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
Igf2 is expressed from the (paternal/maternal) allele, while H19 is expressed from the (paternal/maternal) allele
Paternal; maternal
When do Igf2 knockouts have reduced size at birth?
If they get the knockout allele from the father
The ICR region between heterologous ____________ and promoter that prevent ___________ activity is called an insulator
Enhancer
What is the mechanism of the methylation of ICR with the binding of CTCF?
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)
Maternal-specific methylation typically silences __________ of long non-coding RNAs located __________ protein-conding genes
Promoters; inside
IncRNA is transcribed (sense/antisense) to Igf2r and Kcnq1
Antisense
How does IncRNA transcription lead to silencing within the imprinted domain?
Antisense transcription interferes with sense transcription
The RNA itself recruits chromatin modification enzymes to silence transcription
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
a. Sperm
b. Sperm
c. Oocyte
How is imprinted methylation maintained?
Factors that bind to ICRs and H3K9 methylation
How does Zfp57 contribute to imprinting maintenance?
Binds to methylated sequence at ICRs and recruits H3K9 methyltransferase SETDB1
Which syndromes are caused by deletion of the entire imprinted domain on chromosome 15?
Prader-Willi and Angelman syndromes
AS is caused by (paternal/maternal) transmission of the deletion and PWS is caused by (paternal/maternal) transmission
Maternal; paternal
What causes Beckwith-Wiedemann Syndrome?
Loss of imprinting at KNCQ1 and IGF2 loci
