Lecture 23

Question 1

What does DNA methylation do?

Answer 1

marks both alleles of genes for silencing during cell specilization

Question 2

What do DNMTs do in DNA methylation?

Answer 2

enzymes that add a methyl group to DNA

Question 3

What is the overall process of DNA methylation?

Answer 3

the DNMT transfers a methyl group from SAM to the 5th carbon of the cytosine ring, forming 5-methylcytosine

Question 4

What is S-adenosylmethionine (SAM)?

Answer 4

a molecule in living cells that acts as the methyl donor in DNA methylation

Question 5

What is monoallelic gene expression?

Answer 5

the phenomenon where only one of the two copies of a gene in a diploid organism is actively transcribed while the other is silenced

Question 6

What is genomic imprinting? Is it random?

Answer 6

phenomenon where the expression of a gene is determined by whether it was inherited from the mother or father, not just the gene sequence itself
Nonrandom

Question 7

What are imprinting control regions (ICRs)

Answer 7

DNA sequences that regulate which parent of origin copy of a gene is expressed in offspring
specific epigenetic marks determine whether paternal or maternal allele will be silenced

Question 8

Where does the mechanism that controls genomic imprinting (DNA methylation) occur?

Answer 8

almost exclusively on cytosine residues found in CpG dinucleotides

Question 9

What is the function of DNMT1 in genomic imprinting?

Answer 9

primary maintenance methyltransferase which copies the specific methylation marks on the parental DNA strand to the newly synthesized daughter strand during replication, ensuring imprints are not lost by copying the methylation status from the old strand to the new one

Question 10

What is the function of DNMT3a in genomic imprinting?

Answer 10

de novo DNA methyltransferase
can add methyl marks to previously unmethylated DNA
ensures that specific genes are expressed differently depending on whether their inherited from the mother or father

Question 11

What is the function of DNMT3L in genomic imprinting?

Answer 11

acts as a regulator that simulates the DNA methylation activity of DNMT3a/b
can’t methylate DNA itself because it lacks the necessary enzyme activating domains

Question 12

What is the function of ZFP57 in genomic imprinting?

Answer 12

master regulator that maintains the epigenetic memory of DNA methylation at imprinting control regions
binds to methylated ICRs to maintain their methylated state though interactions with DNA methyltransferase

Question 13

What is the function of ZFP445 in genomic imprinting?

Answer 13

protein that acts as a key regulator by binding to and maintaining ICRs
ensures that only one parental copy of a gene is expressed by cooperating with another protein (ZFP57) to control DNA methylation at ICRs

Question 14

Where and how is imprinting maintained?

Answer 14

in the somatic cells of adults by the DNA methyltransferase DNMT1

Question 15

How is imprinting reprogrammed or “reset”?

Answer 15

In the germline during embryogenesis by global erasure of the DNA methylation marks and histone modifications in the primordial germ cells (precursor cells of sperm and eggs)

Question 16

What happens after imprinted genes acquire different marks in the sperm and egg?

Answer 16

the DNA methylation marks are then heritable through subsequent cell divisions

Question 17

What happens after fertilization?

Answer 17

another round of global demethylation where the DNA methylation patterns are erased on both parental genomes but the ICRs retain parent specific DNA methylation

Question 18

What protects ICRs from demethylation?

Answer 18

ZFP57 and ZFP445
ICRs have several binding sites for these proteins

Question 19

How are DNA methylation and assocated differences in chromatin read after fertilization to ensure that the correct allele is expressed?

Answer 19

differential expression of long non coding RNA
Blocking of an enhancer by an insulator
altered chromatin structure in gene promoter

Question 20

What does differential expression of a long non coding RNA involve?

Answer 20

changes in its abundance (increase or decrease) between different conditions which in turn leads to altered cellular processes by regulating gene expression

Question 21

What is an example of differential expression of a long non coding RNA? Why?

Answer 21

insulin-like growth factor 2 receptor (Igf2r) locus
Igf2r is only expressed from the maternal side (where DNA is methylated)

Question 22

What is an example of blocking an enhancer by an insulator?

Answer 22

Igf2-H19 locus on chromosome 7
Igf2 is paternally expressed (growth factor that simulates placental and fetal growth) and H19 is maternally expressed (regulatory RNA)

Question 23

What is Beckwith-Wiedemann Syndrome? What happens in infants with it?

Answer 23

biallelic expression of Igf2
likely to develop abdominal wall defects, various types of malignant tumors, and enlarged tongue

Question 24

How does the loss of imprinting of Igf2 lead to cancer?

Answer 24

it inhibits apoptosis which promotes cell proliferation

Question 25

What is an example of altered chromatin structure in gene promoter?

Answer 25

Prader-Willi syndrome (PWS)/Angelman Syndrom (AS) locus

Question 26

How does Prader-Willi Syndrome occur?

Answer 26

when the parental allele(s) that would normally be expressed are "missing"

Question 27

How does Angelman Syndrome occur?

Answer 27

when the maternal allele(s) that would normally be expressed are "missing"

Question 28

How are variant and typical methylation patterns detected?

Answer 28

Bisulfite-PCR method for distinguishing cytosine from 5-methyl cytosine

Question 29

What is uniparental disomy (UPD)?

Answer 29

a genetic condition where a person inherits two homologous chromosomes from a single parent instead of one from each parent