Transcription control in disease and evolution

Question 1

Transcription factor p53

Answer 1

A tumour suppressor protein
- Mutations in the gene for p53 are found in 50% of human cancers
- Majority of remaining 50% have mutations that affect p53 function

Question 2

Tamoxifen - Treating breast cancer

Answer 2

• Binds to estrogen receptor inhibiting its function
• The receptor is a transcription factor that turn on the transcription of genes in response to estrogen

Question 3

Rett Syndrome

Answer 3

• Neurodevelopmental disorder
• X-linked dominant mutation affecting 1 in 10000-15000 F births
• Due to de novo mutations in transcription factor, MeCP2, that binds methylated DNA + represses transcription

Question 4

The prodynorphin gene + evolution

Answer 4

• Dynorphin is involved in learning + memory, experience of pain, social attachment + bonding
• Levels of Dynorpin are higher in humans due to diff. in chancer between humans + great apes and other mammals

Question 5

Forelimb length + Transcription factors

Answer 5

• Bats have longer forelimbs than mice
• Increased forelimb length is partly due to increased expression of transcription factor, Prx1

Question 6

Burrowing behaviour in deer mice

Answer 6

Changes in burrowing behaviour in diff species is due to diffs in promoter sequences

Question 7

Transcriptional activity of MAOA gene + aggressive behaviour

Answer 7

• Promoter polymorphisms in MAOA gene together with psychosocial factors are linked to aggressive behaviour
• Psychosocial factors affect epigenetics processes in brain
• 3 repeats + psychosocial factors = violent behaviour

Question 8

Epigenetics + memory - De/methylation

Answer 8

• DNA methylation + demethylation is required for memory formation + consolidation

Question 9

Epigenetics + memory - Histone acetylation

Answer 9

• Plays important role in long-term memory + cognition

Question 10

Epigenetics + memory - Hypoacetylation

Answer 10

Found in neuro-degenerative diseases

Question 11

Rubinstein-Taybi Syndrome

Answer 11

• Due to mutation in a gene that codes for a protein that acetylates histones
• Causes severe learning disabilities

Question 12

Neurodegenerative brain diseases (NBDs)

Answer 12

• Common genetic variants can contribute to risk of diff. diseases
• Many of the variants are not within coding sequences + function by altering gene expression

Question 13

Alzheimer disease + transcriptional repressor REST

Answer 13

• Linked to cognitive impairment + AD
• REST is required in the embryo for neuronal development + then inactivated in mature neurons
• Ageing results in expressing REST that represses genes linked to neuronal cell death by deacetylating histones + adding repressive methylation marks to histones
• Lost of REST activity is linked to AD