Steroid Hormone Receptor Signalling

Question 1

What is special about steroid hormones

Answer 1

They are lipid soluble meaning they can enter the cell and bind to receptors inside the cell

Question 2

What is special about cytoplasmic receptors

Answer 2

They directly control gene expression by going to the nucleus and binding dna

Then they recruit coactivators and corepressors

Question 3

What are the transcription factors domains

Answer 3

DNA binding domain

Transactivation domain

Also could have ligand binding domain

Question 4

What is the dna binding domain

Answer 4

It binds to specific dna sequences (response elements) in a gene promoter

Question 5

Steroid hormone receptors have

Answer 5

DNA binding domains

This is why they’re diff from regular receptors since they are receptors and transcription factors

Question 6

What is the transactivation domain

Answer 6

A part of the transcription factor/steroid hormone receptor that activates transcription

Question 7

What is the ligand binding domain

Answer 7

A domain on the nuclear receptor to that ligands bind to activate it, then it can lead to nuclear translocation

(Moving the receptor to the nucleus)

Question 8

What is an example of a steroid hormone receptor

Answer 8

Glucocorticoid receptor with its ligand cortisol which is a steroid hormone

Cortisol can pass through the membrane to bind to the Glucocorticoid receptor in the cytoplasm.

Then together they go into the nucleus and act as transcription factors for a gene

Question 9

Before the receptors ligand is present, what is the steroid hormone receptor interacting with

Answer 9

It interacts with a chaperone protien to prevent inappropriate interactions of the receptor with different protiens

Once the ligand binds, the chaperone falls off

Question 10

What is an example of a chaperone protien

Answer 10

The HSP90

(Heat shock protien 90)

Question 11

What does the glucocorticoid receptor bind to

Answer 11

The glucocorticoid response element (GRE) which is palindromic (both dna strand have same 5’ to 3’ sequence)

Question 12

What type of protien is the GC receptor

Answer 12

A zinc finger protien

Question 13

What is a zinc finger protien

Answer 13

The receptor has zinc ions that are in between two cysteines and two histidines

These form aplha helices that act as fingers to project into the major groove of the dna

Question 14

How is transcription activated through the use of steroid hormone receptors

Answer 14

To activate the the GC receptor, cortisol binds to it then it binds to dna through the zinc finger motif

Then the active GC receptor binds to the dna and recruits the coactivator CBP

CBP is a histone acetyltransferase which acetylates the histones of the nucleosome

Question 15

What happens once the histone in transcription activation are acetylated

Answer 15

The acetylated histones recruit SW1 / SNF chromatin remodeling complex

The SW1 / SNF disrupt the dna interactions with the nucelosome by sliding the nucleosome of bumping them off the dna

Question 16

After SW1 / SNF displaces the histone what happens

Answer 16

The transcriptional machinery and rna pol 11 can bind to the dna for transcription

Question 17

Steroid receptors can be

Answer 17

Transcription repressor

Transcription activators

Question 18

How is transcriptional repression done

Answer 18

The repressor (could be a steroid receptor) recruits a corepressor that recruits a HDAC

Then the histones in that area are deacetylated and transcription is repressed

Further recruitment of methyl transferase happens

Question 19

In transcriptional repression what happens after the methyl transferase is recruited

Answer 19

It methylated lysine 9 of histone 3 (H3K9)

This leads to the inactive chromatin and silence of genes

Question 20

What are examples of corepressors

Answer 20

NCoR and SMRT

Question 21

How can steroid hormone receptors reprogram cells

Answer 21

They act as transcription factor to repress or activate transcription

So it take for example a neural stem cell to then reprogram it to a mammary stem cell