Epigenetics

Question 1

What is the nucleosome?

Answer 1

Building block (primary unit) of chromatin, made up of DNA-wrapped histones.

Question 2

Where do most of the modifications occur in histones?

Answer 2

In the histone tails.

Question 3

Which common histone modifications change the charge on the amino acid?

Answer 3

serine and threonine phosphorylation and lysine acetylation.

Question 4

How does acetylation activate transcription?

Answer 4

By removing the positive charge on the histone tails, the tails are no longer attracted to the negatively charged phosphate backbone, causing them to unwind.

Question 5

How does modification change regulation of specific sequences?

Answer 5

targets specific sequences and creates binding sites for proteins that recognize the modifications.

Question 6

Where does most DNA methylation occur?

Answer 6

at CpG dinucleotides

Question 7

What are writers?

Answer 7

Enzymes that acetylate or methylate sequences. HATs (histone acetyl transferases), HMTs (histone methy transferases), and DNMTs (DNA methyltransferases.)

Question 8

What are erasers?

Answer 8

Enzymes that remove acetyl groups or methyl groups from sequences. HDACs (histone deacetylases), demethylases.

Question 9

Methylation typically silences genes, how does it do this?

Answer 9

Makes DNA less available by curling up histone tails and DNA tightly, then recruiting other silencing proteins, methyl binding proteins, as well as removing the activating marks

Question 10

How is imprinting achieved?

Answer 10

during germ cell formation, genes are demethylated, then sex-specific patterns of methylation are laid down.

Question 11

What is the typical mutation that leads to Prader-Willis Syndrome and Angelman’s Syndrome? What is another possible cause?

Answer 11

Deletion of 4-5 million break points on chromosome 15. Another possible cause could be abnormal methylation or uniparental disomy.

Question 12

What is the cause of PWS?

Answer 12

Disruption of any of the genes in the PWS critical area. Copy of allele from father is non-functional/mutated, and mother’s allele is imprinted at this area.

Question 13

What is the cause of AS?

Answer 13

Loss or mutation of ubiquitin pathway (degradation pathway). Maternal allele is non-functional and the father’s allele is imprinted.

Question 14

What is X-inactivation?

Answer 14

One of the X-chromosomes is silenced so that genetic material is not duplicated in females.

Question 15

How can a heterozygote female with an X-linked disease allele express the disordered phenotype?

Answer 15

Could express the disease if properly functioning allele is on the silenced X-chromosome.

Question 16

How does X-inactivation happen/what molecules are needed?

Answer 16

X chromosomes are counted, then one is chosen (non-coding RNAs Xist and Tsix are needed, and Xist silences the chromosome.

Question 17

What is the role of Xist?

Answer 17

Physically coats the X-chromosome to silence it.

Question 18

What is the role of Tsix?

Answer 18

Inhibits the action of Xist, therefore preventing silencing.

Question 19

What happens with Xist and Tsix during X-inactivation?

Answer 19

Tsix is inactivated on the chosen X-chromosome, so that it no longer inhibits Xist, which can then coat the chromosome to silence it.

Question 20

What is facultative heterochromatin?

Answer 20

when regions of euchromatin (major genes that are most actively transcribed) are converted into heterochromatic (silent) state. This means it has potential for gene expression at some point in development and can be either condensed or decondensed depending on cell type.