Biochemistry and Molecular Biology II – Lecture 4: Transcriptional control of
gene expression #3
24-04-2018
How does gene expression respond to environmental clues and how does gene
expression control development/differentiation and homeostasis?
Nuclear hormone receptors: receptors for lipid-soluble hormones within the cell.
Contain a ligand binding domain for Estrogen/Tamoxifen (antagonist of estrogen,
counteracting the effects of estrogen).
There are two major types of nuclear hormone receptors:
1. Type I receptors:
Act as homodimers
Glucocorticoid receptor migrates to the nucleus upon ligand binding and activates
anti-inflammatory genes.
When hormone enters cell and attaches to ligand binding domain (LBD) NLS
the signal + glucocorticoid receptor migrates to the nucleus altering the GRE
(glucocorticoid response element) sequence.
When ligand (hormone) is not present, there is repression/inhibition by heat-shock
proteins (chaperones).
2. Type II receptors:
Act as heterodimers
e.g. TR/RXR and RAR/RXR
These proteins are already sitting on the promoters, but the co-repressor is recruited,
inhibiting transcription.
When hormone (ligand) enters the cell conformational change occurs, releasing
the co-repressor and replacing it with the co-activator + RNA-polymerase this then
results in synthesis of mRNA.
In absence of ligand: repression of transcription.
In presence of ligand: activation of transcription.
*Most signal transduction pathways regulate transcription factors
Post-translational modifications on transcription factors is a major regulatory step:
e.g. phospohorylation (ser, thr), acetylation (lys), glycosylation (ser, thr),
ubiquitination (lys) these PTMs lead to e.g. nuclear localization,
stability/degradation, etc.
Heat shock response:
Heat shock response is regulated by the TF: HSF (Heat-shock factor)
- When there is no stress: HSF + HSP90 are in the cytoplasm
gene expression #3
24-04-2018
How does gene expression respond to environmental clues and how does gene
expression control development/differentiation and homeostasis?
Nuclear hormone receptors: receptors for lipid-soluble hormones within the cell.
Contain a ligand binding domain for Estrogen/Tamoxifen (antagonist of estrogen,
counteracting the effects of estrogen).
There are two major types of nuclear hormone receptors:
1. Type I receptors:
Act as homodimers
Glucocorticoid receptor migrates to the nucleus upon ligand binding and activates
anti-inflammatory genes.
When hormone enters cell and attaches to ligand binding domain (LBD) NLS
the signal + glucocorticoid receptor migrates to the nucleus altering the GRE
(glucocorticoid response element) sequence.
When ligand (hormone) is not present, there is repression/inhibition by heat-shock
proteins (chaperones).
2. Type II receptors:
Act as heterodimers
e.g. TR/RXR and RAR/RXR
These proteins are already sitting on the promoters, but the co-repressor is recruited,
inhibiting transcription.
When hormone (ligand) enters the cell conformational change occurs, releasing
the co-repressor and replacing it with the co-activator + RNA-polymerase this then
results in synthesis of mRNA.
In absence of ligand: repression of transcription.
In presence of ligand: activation of transcription.
*Most signal transduction pathways regulate transcription factors
Post-translational modifications on transcription factors is a major regulatory step:
e.g. phospohorylation (ser, thr), acetylation (lys), glycosylation (ser, thr),
ubiquitination (lys) these PTMs lead to e.g. nuclear localization,
stability/degradation, etc.
Heat shock response:
Heat shock response is regulated by the TF: HSF (Heat-shock factor)
- When there is no stress: HSF + HSP90 are in the cytoplasm
