Differentiation 3 - What regulates the regulators

Question 1

Name 2 ways to regulate TFs

Answer 1

• control their activity (protein modifications)
• control their expression (other TFs)

Question 2

What are TFs regulated by?

Answer 2

• environmental signals (signals)
• developmental history (early TFs regulate later TFs)

Question 3

Explain regulation by phosphorylation

Answer 3

• post translational modification
• kinase enzymes
• phosphates are large and negatively charged
• can either activate or inhibit TF

Question 4

explain how growth factors regulate gene expression via phosphorylation of TFs

Answer 4

• Epidermal growth factor (EGF) is a mitogen
• binds to EGF receptors
• phosphorylation of MYC (bHLH-LZ TF) on serine and threonine residues (Ser-62)
  stabilises the MYC gene and drives transcription of cyclin genes

Question 5

What is a mitogen?

Answer 5

induced cell division and promotes cell proliferation

Question 6

What is a phospho-null mutation?

Answer 6

mutation an amino acid able to be phosphorylated to one that isn’t (removal of an -OH)

Question 7

What is a phosphomimetic mutation?

Answer 7

one that resembles a phosphorylated amino acid

Question 8

Explain phosphorylation of GATA1 in red blood cell differentiation

Answer 8

• kidney secretes the hormone erythropoietin (EPO)
• in bone marrow, binding to EPO receptor simulates progenitor proliferation and red blood cell proliferation
• EPO causes phosphorylati9on of GATA1, increasing its DNA binding affinity
• low O2 - greater EPO secretion

Question 9

What are red blood cell progenitors?

Answer 9

proerythroblasts

Question 10

why is it important that TFs are regulated by other TFs?

Answer 10

• orderly progression through to differentiation
• control of cell fate choice

Question 11

Explain the differentiation process forming plant leaf stomata

Answer 11

• protoderm cell (leaf progenitor)
• SPCH TF activates genes forming meristemoid cells
• MUTE TF activates genes forming guard mother cells
• FAMA TF activates genes forming guard cells
• if SPCH is not expressed then cells will follow the default pathway to form pavement cells

Question 12

What part of the mesoderm forms the myotome?

Answer 12

somite

Question 13

Name the TFs and signals in the muscle differentiation pathway

Answer 13

bHLH TFs
- MyoD
- Myf5
- Mrf4
- Myogenin
paired box homodomain TF expressed in somite
- Pax 3
Regulatory signals
- Wnt
- SHH
- BMP

Question 14

Explain the muscle cell differentiation pathway

Answer 14

Activation of MoD gene
- SHH activates Myf5
- Myf5 binds to E box and Pax 3 binds to Pax site
- MyoD is expressed

Autoregulation of MyoD
- MyoD then binds to its own E box, regulating its own transcription
- Myf5 and pax 3 are no longer needed for MyoD expression

Regulation of MyoD protein stability
- growth factors promote cell division
- CDKs phosphorylates MyoD and Myf5
- these are then degraded
- whole growth factors are present, muscle differentiation is inhibited

Pax3 mRNA degradation
- pax3 required for early muscle development
- down regulated for later stages to happen
- mRNA is degraded by microRNA miR-1 interference