Transcription factors Flashcards
What is meant by Gene expression ?
DNA undergoes TRANSCRIPTION to form RNA which translates to PROTEIN
What is meant by the ‘Central Dogma’ ?
DNA makes RNA makes PROTEIN (Crick)
What are Eukaryotic RNA Polymerases and how many types are there?
- Enzymes that perform transcription (of genetic information) from DNA to RNA.
- 3 types of Eukaryotic RNA Polymerases
Where are the RNA Polymerases located ?
Nucleus
What is the function of RNA Polymerase I
To transcribe rRNA (rRNA is essential for transcription)
What is the function of RNA Polymerase II
To transcribe …1) Eukaryotic genes 2) Protein encoding genes (mRNA)
mRNA = translated into Protein and genes for regulatory genes e.g; miRNA
What is the function of RNA Polymerase III
To transcribe structural RNAs
Name 3 examples of structural RNA ?
1) 5S pre-RNA
2) pre-tRNA
3) snRNA
What is a ‘Transcription factor’ ?
A protein that binds to DNA and helps recruit the appropriate polymerase. Therefore controls the rate of transcription of genetic information from DNA to RNA
How do TF’s help to recruit the appropriate polymerase?
1) One or more TF binds to DNA regulatory sequences
2) Recruits co-factors
3) Therefore; allows efficient recruitment of DNA Polymerase
Name 3 examples of co-factors ?
1) Activators
2) Co-activators
3) General factors
What is the role of Activators ?
1) Bind to DNA at ENHANCERS
2) DNA folds and enhancer = brought into contact with INITIATION COMPLEX
3) Activator proteins interact with initiation complex therefore INCREASES RATE OF TRANSCRIPTION
What is the role of Co-Activators ?
Transmits signals from activator proteins to general factors
What is the role of General factors ?
Initiates Transcription. by;
1) Positioning RNA polymerase at start of protein-coding sequence
2) then; releasing the polymerase to initiate transcription
What is Estrogen ?
Type of steroid hormone (female sex hormones & corticosteroids)
Role of Cholesterol in producing Estrogen ?
1) Cholesterol = modified by enzymes to make steroid hormones (Estradiol) in the ovaries
Name 3 types of Estrogen and which is the most potent in the body ?
1) Estrone (E1)
2) Estradiol (E2) = Most potent
3) Estriol (E3)
What does the Estrogen- receptor complex bind to?
A 38-base pair estrogen responsive element (ERE) consensus sequence.
What does the (ERE) consensus sequence contain ?
The inverted repeat; 5’-GGTCAnnnTGACC-3’ - this causes gene expression
Name the primary function of Estrogen
For development of the female secondary sexual characteristics. e.g; Breasts, Endometrium, Menstrual cycle AND for Stimulation of cell Proliferation
Name 4 organs Estrogen has an effect on
1) Bones
2) Brain
3) Heart
4) Liver - Increases good cholesterol (HDL), Decreases bad cholesterol (LDL)
What are the 2 types of Estrogen receptors and where are they located?
ERalpha (coded for by ESR1) and ERbeta(coded for by ESR2) - they are located on seperate chromosomes
What is the action of Estrogen in the cell dependent upon ?
On the presence/type of estrogen receptor on the target cell
In what tissues/cells can ERa be found ?
Endometrium, Hypothalamus, Breast cancer cells, Ovarian Stroma cells
In what tissues/cells can ERb be found ?
Bone, Brain, Heart, Kidney, Lungs, Intestinal mucosa, Prostate, Endothelial cells
What are some harmful effects of Estrogen ?
Increases risk of cancer in the Breast and Uterus
What are Antiestrogens ?
Estrogen antagonist that inhibit estrogen binding
What are SERMs ?
Selective Estrogen Receptor Modulators -can act as Agonists and Antagonists
Why is the structure of ligand bound to the ER important ?
Dependent on the structure, this influences the ability of the ER to interact w/other transcriptional co-factors
Name 3 types of major SERMs
1) Tamoxifen
2) Raloxifene (a new SERM)
3) Clomifene
Uses of Tamoxifen ?
ER Antagonists - Inhibits estrogen-dependent growth, of breast cancer (In breast tissue)
Partial Agonists - In Bone and Uterus endometrium - Stimulates growth
Risks of Tamoxifen ?
1) Binds to ER causing endometrial cell proliferation = increase cancer risk
2) Increases risk of blood clot
Uses of Raloxifene ?
Antagonists -In Breast and Endometrium - reduces cancer risk
Agonists - In Bone - Decreases bone resorption = Osteoporosis treatment
Uses of Clomifene ?
Antagonists -In Hypothalamus and Anterior pituitary gland - Increases release of Ovulation hormones
Agonists - In Ovaries - Treatment for Infertility
