Lec1/2: Transcriptional Control Flashcards
what is RNA pol 1 used for?
Ribosomal RNA genes
What is RNA pol 2 used for?
Protein coding genes, miRNAs and non-coding RNAs
What is RNA pol 3 used for?
tRNAs
Where is an enhancer located?
-1000bp
Where are Upstream Sequence elements (USE) located?
-100bp
Where is TATA box located?
-30bp (-28,-32)
Where are initiator elements located?
+1bp
What are initiator elements?
Adenine base flanked by pyrimidine sequence. (YYANYAYY)
What happens at the TATA box?
Where RNA pol 2 interacts but through proteins not directly
How is an initiator complex assembled?
-TF2D binds TATA box (90 degree angle in DNA
-TF2D bound by TF2A
-TF2B also binds TF2D
-RNA pol 2 recruited and comes with TF2F attached
-TF2E and TF2H bind as well
What is TF2D?
TATA binding protein (TBP)
What is TF2A function?
Stabilises TF2D and DNA interaction
What is TF2B function?
To recruit RNA pol2
What is TF2E function?
Functions as an ATPase to supply energy
What is TF2H function?
Helicase
What is TF2F function?
Comes prebound to RNA pol2
What is the pre-initiaton-complex (PIC) made up from?
TF2A,B,D,E,F,H and RNA pol2
What is difference with TATA less promoters?
They have DPE (downstream promoter elements) instead of TATA box but also still has initiator sequence
What is DPE downstream promoter elements sequence and where is it located?
AGAC (+28-+32)
What Transcription factor changes in TATA less promotion?
They use TF2I instead of TF2D
What is focused transcription initiation?
Focused is usually highly conserved genes that have a TATA box
What is dispersed transcription initiaton?
Dispersed usually has DPE (downstream promoter elements) and are constitutively conserved.
What are the two types of transcription iniitiation?
Dispersed and focused
What has a large effect on the level of transcriptional control?
Transcription factors that bind upstream of TATA/INR
What types of TFs are there?
-confer general transcription
-confer tissue specific transcription
-confer inducible transcription
Example of TFs that confer general transcription?
SP1
Example of TFs that confer tissue specific transcription?
MyoD and Oct-2
Example of TFs that confer inducible transcription?
CREB and Esteogen receptor
What are enhancers?
Where TFs bind to. activate transcription can be placed 1000sbp away its orientation doesn’t matter and can be up or downstream
How do enhancers work?
They form a loop brining the Transcription factor to the pre-initiation complex.
What are silencers?
Area of genetic code that Can act 1000s if base pairs away and loop to Pre-initiation complex but repress expression all control.
What are insulators?
Molecules that control the activity of enhancers and silencers
How do insulators control expression?
By blocking interaction between enhancers,silencers and PIC
Where are insulators located?
Between enhancers/silencers and their promoters
Where are insulators found?
Between silencer/enhancers and promoters
What makes up LCR?
Made of enhancers and silencers and promoters
What is the LCR?
Locus control region
What does TAD stand for?
Topologically associated domain
What are TADs?
Large multi component domains that facilitate long range interactions. Allow for control of gene expression by restricting chromatin reactions
What does LADs stand for?
Lamellar associated domain
What are LADs?
Areas of DNA consisting of transcription ally silent chromatin enriched with lys27 on histone H3
What happens to if TADs are disrupted?
Result in altered gene expression and can cause genetic disease or cancer.
What’s the structure of a TF?
A modular structure
What is a modular structure?
This means all AAs involved in binding are in one place.
What is a homeodomain?
-transcription factor binding domain
-60 residue, 3 helix domain. Helices 2 and 3 form helix-turn motif.
What are zinc fingers?
-transcription factor binding domain
-motif that uses 2x cystine and 2x histidine to hold the zinc forming finger like domain
Where do you u find homeodomains?
Tend to be found in development control genes for example HOX genes
Where do you find zinc finger domains?
Found in the major groove of DNA, usually used by steroid hormone receptors to bind DNA.
Give an example of basic binding domain?
Leucine zipper
What are leucine zippers?
-transcription factor binding domain
-basic basic being domains
-alpha helix with leucine residue every 7 residues
What’s the structure of leucine zippers?
-They are dimers
-3 types of monomers allowing for 6 different dimer combinations
What are activation domains?
Domains that bind and work through interaction with the PIC.
Can work through mediators after PIC binding
What are the 3 methods of inhibitory transcription domains?
-competition
-quenching
-recruitment of co-repressors
How do competitive TFs work?
Through competition of repressor and activator proteins
How does quenching inhibition work?
Type 1: repressor binds and blocks DNA binding region of an activator
Type2: Repressor binds to and blocks activation domain of an activator
Examples of co-repressors inhibitory TFs recruit?
Mad recruits NCoR + Sin3A
Wha ya the key role of TFs?
-Regulate differentiation and tissue specific gene expression
-for example MyoD in muscle cells
