Gene Regulation, Evolution and Disease

Question 1

Describe the difference of retinoic acid in mice and humans.

Retinoic acid

Answer 1

Humans have a higher level of retinoic acid in the brain than mice, specifically in the prefrontal cortex as that indicates that there is an increase in transcription of genes associated with RXRG and RARB, and a higher density of dendritic spines on PFC neuronal cells.

Question 2

List epigenetic causes for disease.

Epigenetics and disease

Answer 2

Transcription factor mutation
Enhancer mutation
Aberrant chromatin modification or remodelling
Altered gene dosage

Question 3

Diseases associated with TAF1 dysfunction.

Epigenetics and disease

Answer 3

Cancer
Cardiac anomalies
X-linked dystonia-parkinsonism
X-linked intellectual disability

Question 4

What can be the result of mutations to TP53?

Epigenetics and disease

Answer 4

TP53 is a gene that encode p53, a tumour supressor gene. Mutations can cause DNA damage, oncogene signalling, nutrient deprivation, hypoxia and ribosomal stress.

Question 5

Describe the altered gene dosage in Down’s syndrome.

Epigenetics and disease

Answer 5

The extra copy of chromosome 21 causes an increased gene dosage of the proteins DSCR1 and DYRK1A.
DSCR1 blocks the action of calcineurin, which dephosphorylates NFAT (a TF), thus preventing it from going into the nucleus.
DYRK1A phosphorylates NFAT in the nucleus, thus causing it to migrate back to the cytoplasm.
Altered gene dosage prevents transcription.

Question 6

Describe the DNA methylation in neurons.

Epigenetics and disease

Answer 6

Neurons have much higher levels of non-CpG cytosine methylation, mCH. It is a unique epigenetic tag that is targeted by MeCP2.

Question 7

Describe epigenetic changes in aging and cancer cells.

Epigenetics and disease

Answer 7

Histone and heterochromatin loss
Increase in histone variants
Aberrant histone mods
Aberrant DNA methylation

Question 8

What is the difference in methylation in aging cells?

Epigenetics and disease

Answer 8

Global hypomethylation, resulting in partially methylated domains (PMDs)

Question 9

What is the difference in methylation in cancer?

Epigenetics and disease

Answer 9

PMDs and hypermethylation of CpG islands, which silence tumour surpressor genes