Cellular differentation
The process by which a cell changes from one type to another. This is a permanent change ( in mamals)
bijv. stem cell to neuron
External stimuli
Can alter gene expression
bijv. growth factor or hormones
1. directly enter the cell
2. Interact with surface receptor
Direct cell permeation
Lipophilic / hydrophobic compounds -> steroid hormones
- Freely diffuse through cell membrane
- Bind to cytosolic receptor in cell and migrate to nucleus
- The hormone-receptor complex acts as TF, binding to DNA hormone response element
Kinase receptors
Transduction of signal is mediated by phosphorylation of cytoplasmic protein
3 main types:
1. tyrosine kinase receptors
2. serine-threonine kinase receptors
3. Kinase-associated receptors
Tyrosine kinase receptors
- Phosphorylate a Tyr residue on the target protein
- Dimers of 2 identical subunits
- Extracellular domain for ligand binding
- Intracellular domain with kinase activity
- Dimers are dissociated -> interaction with the ligand promotes dimerization -> activating kinase activity.
MAP kinase pathway
- an inactive G-protein (Ras bound to GDP) anchored to protein close to mitogen receptor
- Mitogen receptor dimerizes in response to mitogen binding
- Dimerization induces self-phosphorylation of the receptor and recruitment of GEF.
- GEF promotes exchange of GDP to GTP -> activitng the G-protein (Ras)
- Ras-GTP is now able to phosphorylate Raf
- Phosphorylated Raf phosphorylates Mek
- Mek now does the same to MAPK
- MAPK translocates to nucleus activating a series of TF (by phosphorylation)
JAK/STAT pathway
- Receptor is associated with the Janus kinase (JAK)
- Interaction of the receptor with a ligand (usually cytokine) stimulates dimerization.
- 2 JAK kinase subunits are brought in close to each other by the receptor dimerization and phosphorylate each other.
- JAK is now active and can phosphorylate STATs
- STATs will now dimerize, allowing translocation to nucleus
- STAT dimer binds to DNA and activates transcription of a specific set of genes.
Blastocyst
- Trophoblast
- Inner cell mass (ICM)
Types of promoters of ESCs
- H3K4me3
- H3K27me3
H3K4me3
Marks active promoters of genes that need to be actively transcribed by the cell
H3K27me3
Marks repressed promoters of genes that must not be transcribed
Bivalency
- present both marks (H3K4me3 and H3K27me3)
- Present in promoters of developmental genes in ESCs
- are not active, nor stably repressed.
- allows ESCs to rapidly activate/deactivate developmental genes as soon as they receive a differentiation stimulus
