cell differentiation 3

what are the 2 main ways that transcription factors are regulated?

by controlling their activity (by protein modifications) and by controlling their gene expression (regulated by other trnascription factors)

what are the 2 factors that regulate transcription factor activity?

environmental signals (hormones, GF etc.) and developmental history (early TFs in cell lineages regulate expression of later TFs)

what are the complex regulatory interactions between TFs called?

gene regulatory networks (GRNs)

how are the transcription factors regulated by cell signalling?

1. the cell sends a signal that binds to receptors on a target cell

2. the signal triggers a cascade 

3. the cascade activates or inhibits a TF

4. this will alter the gene expression

how can the TF activity be regulated by phosphorylation?

• phosphorylation will alter the protein conformation

• this can activate or inhibit the TF

• this is carried out by kinase enzymes using ATP and can be reversed by phosphatases

• the phosphate groups can prevent the DNA from binding

how do growth factors regulate gene expression via phosphorylation of TFs?

• the growth factors active a protein kinase cascade

• MAP kinase enters the nucleus and phosphorylates the TFs which activates them

• RAF—> MAPKK—>MAPK

  • this results in activation of target gene expression

how does the epidermal growth factor (EGF) affect transcription?

• EGF will bind to a receptor which phosphorylates the MYC (bHLH-LZ TF)

• the phosphorylation stabilises the MYC which drives cyclin gene transcription and cell proliferation

• the mutated MYC can become constantly active which leads to cancer formation

what is the role of GATA1 in red blood cell differentiation?

• the hormone EPO (in the kidney) binds to receptors on progenitors in the bone marrow

• this stimulates proliferation and erythropoiesis

• EPO causes GATA1 phosphorylation which increases DNA binding affinity

what happens when there is low O2 in humans?

theres increased EPO so increased phosphorylated GATA1 which will activate red blood cell differentiation

what is the function of MyoD in muscle differentiation?

it regulates muscle specific gene expression and coordinates activation of muscle target genes

why is the transcription factor gene expression tightly regulated ?

it ensures orderly progression through differentiation and it controlls cell fate choices

signals can also activate TF cascades which leads to terminal differentiation

what is the function of lead stomata?

they are found on the leaf surface for gas exchange

the guard cells open and close stomata via osmosis

mRNA for KAT1 potassium channel protein is expressed in guard cells

what is the lineage pathway for leaf stomata guard cell differentiation?

1. protoderm (leaf progenitor)

   1. default —> pavement cell

   2. alternative —> meristemoid mother cell by asymmetric division

      1. meristemoid—> guard mother cell—> divides symmetrically—>guard cells

what are the transcription factors that regulate stomatal differentiation in plants?

Spch - protoderm —> meristemoid mother cell

MUTE - meristemoid —> guard cells

FAMA - guard mother cell —> guard cells

what are the steps of muscle differentiation (myogenesis)?

• in paraxial mesoderm —> forms the somite

• somite —> myotome (under WNT,SHH, BMP. signals)

• mesodermal progenitors —> myoblasts (use growth factors)

• loss of growth factors —> multinucleate myotubes —> muscle fiber (MyoD regulated)

what are the transcription factors involved in muscle differentiation?

bHLH family (MyoD, Myf5 , Mrf4) , Paired box TF (Pax3), regulatory signals (GF, WNT , SHH, BMP)

how is the MyoD gene regulated within the gene regulatory network (GRN)?

there is myoblast formation due to SHH signals

MyoD expression is regulated by Pax3 and Myf5 

what occurs in MyoD gene activation?

if pax 3 is present —> proceed

if Myf5 is activated —> Pax3 + Myf5 —> MyoD on

how does MyoD autoregulate its own expression?

• its activated initially by Pax3 and Myf5

• MyoD activates its own genes —> positive feedback

• MyoD expression becomes independent—> cell memory

how is MyoD protein stability regulated?

• GF promote proliferation

• CDKs phosphorylate MyoD and Myf5 —> proliferation, inhibits differentiation

• proteolytic degredation stabilises MyoD after GF removed

• differentiation occurs once GF decline

what happens to Pax3 mRNA during differentiation?

• Pax3 defines the early somite and early muscle differentiation

• it must be downregulated later

• degraded by microRNA miR-1 via RNA interference

• removal allows later stages of differentiation to proceed