Lecture 10 - Transcriptional Regulation 2 Flashcards
Promoter
Sequence of DNA near the 5’ end of the coding region of a gene where RNA polymerase binds and initiates transcription
Two important sequences in a promoter
- Recognition sequence
2. TATA box
Recognition sequence
The sequence recognized by RNA polymerase
TATA box
Called this because it is rich in AT base pairs. Sequence closer to the transcription initiation site where DNA begins to denature so that the template strand can be exposed
Transcription cannot start until what happens
Until transcription factors have assembled on the chromosome
Explain what happens before RNA polymerase II can bind
- Transcription factor TFIID binds to the promoter at the TATA box changing its own shape and that of the DNA
- Other transcription factors join it to form a transcription complex
- RNA polymerase II binds only after several transcription factors are already bound to DNA
Enhancers
Positive regulators which bind activator proteins
Silencers
Negative regulators which bind repressor proteins
What determines the rate of transcription?
Efficiency of binding of GTFs to the core promoter DNA sequences determines levels of transcription (promoter strength)
Remodelling of chromatin
Increases the accessibility for trancription
Transcriptional regulation
Controlling when and how often a given gene is trancribed
RNA Processing control
Controlling the splicing and processing of RNA transcripts
RNA transport and localisation control
Selecting which completed mRNAs are exported from the nucleus to the cytosol and determining where in the cytosol they are localized
Translational control
Selecting which mRNAs in the cytoplasms are translated by ribosomes
Post-translational modification
Control of protein like phosphorylation, acetylation, ubiquitination of them
Protein activity control
Selectively activating, inactivating, degrading, or localizing specific protein molecules after that have been made
Core promoter binding sites for TFIIB
TFIIB can bind the BRE elements
Core promoter binding sites for TFIID
TBP subunit of TFIID can bind the TATA box
mRNA degradation control
Selectively destabilizing certain mRNA molecules in the cytoplasm
Transcription regulators
Recognize specific sequences of DNA that are often called cis-regulatory sequences. This binding ultimately specifies which genes are to be transcribed and at what rate
cis-regulatory sequences
They must be on the same chromosome (in cis) to the genes they control
What do transcriptional activators or repressors do?
They bind to DNA regulatory elements (promoter proximal or distal sequences) and either enhance or repress transcription levels directed by the basal transcription factors and RNA polymerase at the core promoter
What type of transcription factors are activators and repressor proteins?
Sequence-specific transcription factors
What can DNA bending do?
It can bring the activator protein, that was bound to an enhancer element far from the promoter, into contact with the transcription complex
Where is the minor groove of DNA?
Occurs where the back bones are close together
Where is the major groove of DNA?
Occurs where the backbones are far apart
Structural motifs
Different combinations of structural elements (protein confirmations) and may include special components such as zinc
Four common structural motifs in DNA binding domains
- Helix-turn-helix
- Leucine zipper
- Zinc finger
- Helix-loop-helix
Criteria for the structure of a protein motif that will recognize an intact DNA double helix
- Fits into the major or minor groove
- Has amino acids that can project into the interior of the double helix
- Has amino acids that can form hydrogen bonds with the interior bases
Helix-turn-helix motif
- Two a-helices are connected via a non-helical turn
- Interior-facing ‘recognition’ helix is the one whose amino acids interact with the bases inside the DNA
- The exterior-facing helix sits on the sugar-phosphate backbone, ensuring that the interior helix is presented to the bases in the correct configuration
What type of proteins have the helix-turn-helix in their structure?
Repressor proteins
What do proteins with helix-turn-helix motifs in their structure do?
They regulate genes involved in development
Transcription factors reach into which groove?
Major groove
What do the proteins with leucine zipper motifs do?
These proteins regulate cell division genes.
Mutation in these give rise to cancer
What do the proteins with zinc finger motif motifs do?
These proteins are steorid hormone receptors
What do the proteins with helix-loop-helix motifs do?
These proteins regulate immune system genes.
Sets cells on the path to become muscle tissue
3 functional domains
- DNA binding domains
- Dimerization doman
- Activation/repression domain
Dimerization domain
Homodimers or heterodimers are formed with other regulatory proteins
Cooperative binding
The arrangement of transcription factor binding sites, such that two different transcription factors can interact, stabilizing each other’s binding to the DNA
How can genes be coordinately regulated by transcription factors?
The expression of genes can be coordinated if they share regulatory sequences that bind the same transcription factors.
Epigenetics
Changes in the expression of a gene or set of genes that occur without changing the DNA sequence
