Transcription factors and Epigenetics

Question 1

What are transcription factors?

Answer 1

Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes, by binding to a specific DNA base sequence on a promoter region

Question 2

Describe how transcription can be regulated using transcription factors

Answer 2

• Transcription factors move from cytoplasm to nucleus
• They bind to DNA at a specific DNA base sequence on a promoter region,upstream of the target gene
• This stimulates or inhibits transcription (production of mRNA) of target genes by helping or
  preventing RNA polymerase binding

Question 3

Explain how oestrogen affects transcription

Answer 3

• Oestrogen is a lipid-soluble steroid hormone so diffuses into
  cell across the phospholipid bilayer
• In the cytoplasm, oestrogen binds to its receptor, an inactive
  transcription factor, forming an oestrogen-receptor complex
• This changes the shape of the inactive transcription factor,
  forming an active transcription factor
• The complex diffuses from cytoplasm into the nucleus
• Then binds to a specific DNA base sequence on the promoter
  region of a target gene
• Stimulating transcription of target genes forming mRNA by
  helping RNA polymerase to bind

Question 4

What is epigenetics?

Answer 4

Heritable changes in gene function / expression without changes to the base sequence of DNA, caused by changes in the environment (e.g. diet, stress, toxins)

Question 5

What is the epigenome

Answer 5

All chemical modification of DNA and histone proteins - methyl groups on DNA and acetyl groups on histones

Question 6

How can methylation and acetylation inhibit transcription?

Answer 6

• Increased methylation of DNA - methyl groups added to cytosine bases in DNA
• So that DNA is wrapped around
  histone more tightly
• Preventing transcription factors and RNA polymerase binding to promoter
• Decreased acetylation of histones
  increases positive charge of histones
• So histones bind to DNA (negatively charged) more tightly
• Preventing transcription factors and RNA polymerase binding to promoter

Question 7

Explain the relevance of epigenetics on disease development and treatment

Answer 7

• Environmental factors (e.g. diet, stress, toxins) can lead to epigenetic changes
• These can stimulate / inhibit expression of certain genes that can lead to disease development
• Increased methylation of DNA or decreased acetylation of histones inhibits transcription
• Decreased methylation of DNA or increased acetylation of histones stimulates transcription
• Diagnostic tests can be developed that detect these epigenetic changes before symptoms present
• Drugs can be developed to reverse these epigenetic changes

Question 8

What is RNA interference (RNAi)?

Answer 8

Inhibition of translation of mRNA produced from target genes, by RNA molecules e.g. siRNA, miRNA. This inhibits expression of (silences) a target gene

Question 9

Describe the regulation of translation by RNA interference

Answer 9

• Small interfering RNA (siRNA) or micro-RNA (miRNA) is incorporated into / binds to a protein, forming an RNA-induced silencing complex (RISC)
• siRNA is synthesised as double-stranded RNA, so 1 strand is incorporated
• miRNA is synthesised as a double-stranded hairpin bend of RNA. so
  both strands are incorporated
• Single-stranded miRNA / siRNA within RISC binds to target mRNA with a complementary base sequence
• This leads to hydrolysis of mRNA into fragments which are then
  degraded or prevents ribosomes binding
• Reducing / preventing translation of target mRNA into protein