Shemanko Lecture 10 Flashcards
What are the three transcription factor domains for steroid hormone receptors?
DNA binding domain: Binds to specific DNA sequences (response elements) in a gene promoter
Trans activation domain: activates transcription
ligand binding domain: binds to the nuclear receptor to activate the receptor, thus can result in nuclear translocation (brings to nucleus)
What is the glucocorticoid receptor?
in a nuclear receptor that includes a ligand-binding domain and dna binding transcription factor
What does the glucocorticoid receptor bind to?
it binds to a glucocorticoid response element (GRE)- is a palindrome (has the same 5’ to 3’ sequence)
What is the chaperone protein HSP90?
Are proteins which bind to steroid hormone receptors, and ensure the receptors retain the proper confirmation under stresses, falls of once ligand binds
What happens once ligand binds to a a steroid hormone receptor generally?
The chaperone molecule falls off, the receptor homodimerizes and then teanslocates to the nucleus, then it binds to the DNA response element with its dna binding domain
What is the zinc finger motif? how does it relate to the glucocorticoid receptor?
The receptor binds to zinc molecules creating finger like projections that go into major grooves in the target DNA
Describe a model for transcriptional activation on the gene promoter?
- The ligand cortisol binds to the glucocorticoid receptor (GR) which activates
- then the receptor binds to the DNA and recruits the coactivator (CBP- justine acetyltrasnferase) which opens chromatin
- The acetylated histones than recruit the SWI/SNF chromatic remodelling complex through epigenetic markers and other proteins
- The SWI/SNF complexes slides the nucleosides and bump them off DNA
- Transcriptional machinery and polymerase 11 then bind for RNA transcription
Describe how transcriptional repression works?
A transcriptional repressor recruits a corepressor or which recruits histone deacetylase and that removes acetyl groups and represses transcription
A methyl transferase gets recruited and methylates H3K9 silencing genes and making chromatin inactive.
What is HP1?
a protein that binds to modified H3K9 after methylation, causing heterochromatin to form
Gene repression occurs through what with type 2 nuclear steroid hormone receptors?
Interactions with NCoR and SMRT core presser complexes that have Histone deacetylases associated
Steroid hormone signal transduction events are critical for what?
Reprogramming cells in the mammary gland