Question

Review the mechanism by which the glucocorticoid hormone activates the transcription of certain genes. What is an “NLS” and how is it involved in the pathway? What kind of regulatory transcription factor (activator?/repressor?) is glucocorticoid receptor and what kind of regulatory element (enhancer?/silencer?) does it bind to? How does glucocorticoid receptor know which genes to influence?

Answer 1

Answer of sub part of question

Review the mechanism by which the glucocorticoid hormone activates the transcription of certain genes. What is an “NLS” and how is it involved in the pathway?

Glucocorticoid receptors are a class of steroid receptors found inside the cell (Not on plasma membrane). When there is no glucocorticoid (ligand), they remain bound by heat shock proteins (HSP90).

Glucocorticoid receptors contain several domains- Regulatory domain, DNA binding domain, hinge region, ligand binding domain etc..

When glucocorticoid diffuses inside the cell through plasma membrane then it binds to receptor and causes conformational changes which in turn does two very important things

1- Release of HSP 90

2. Release of HSP 90 exposes a particular area in the hinge region of receptor which containd Nuclear localization signal (NLS). Exposure of NLS triggere movement of receptor to nucleus from cytoplasm.

Sub part of question-What kind of regulatory transcription factor (activator?/repressor?) is glucocorticoid receptor . what kind of regulatory element (enhancer?/silencer?) does it bind to

These receptors are involved in both activtion and repression of different genes

After translocation via active transport into the nucleus, and binding to specific DNA responsive elements it activates gene transcription. This mechanism of action is referred to as transactivation. It mainly upregulates the expression of anti-inflammatory proteins in the nucleus.

Activated GR can bind with some transcription factors like NF-κB or AP-1 and inhibit their binding to DNA and hence repress the activity of genes which would have been otherwise activated with free NF-κB and AP-1. Itis called trans repression .

Like any other transcription factor bound GR also have recognition site on DNA where it attches to only at particular site and triggers it's transcription. The preferres gene also depends upon the type of cell where it is present.