Lesson 4 of 5 / Genomes and gene regulation
Switch transcription up or down
How can a distant enhancer influence a promoter?
In this lesson: Explain promoters, enhancers, silencers and transcription factors.
About 6 min
The key ideaDNA control elements bind proteins that recruit or inhibit transcription machinery; DNA looping can connect distant sites.
Explore the idea
Connect the enhancer to the promoter
The enhancer is a DNA element. Its activator is a protein. Looping can bring that bound activator into contact with the transcription complex and increase initiation.
Illustrative matched reporter constructs and arbitrary RNA units. The purple shape represents the activator. Normalise delivery and cell number; restoring the enhancer would strengthen the causal interpretation. A silencer-bound repressor can instead reduce expression through its regulatory interactions.
Explanation
A promoter positions transcription machinery for a gene. General transcription factors and RNA polymerase form an initiation complex. Regulatory transcription factors bind particular DNA control sequences, allowing a cell to respond selectively rather than turning every gene up together.
An activator bound to an enhancer can interact with proteins at the promoter through a loop in the DNA, increasing initiation. A repressor can bind a silencer or interfere with activation, reducing transcription. The control element is DNA; the activator or repressor is a protein, so they are not interchangeable terms.
Different cells contain different combinations or activities of transcription factors. A muscle cell and a nerve cell can therefore transcribe different genes even with the same genome. A signal can change a factor's activity, producing temporal control without requiring a new mutation.
A reporter experiment can test a regulatory sequence by comparing otherwise matched constructs, one with an intact element and one altered. Include a normalisation control for cell number and delivery. Less reporter signal is evidence of changed expression, but protein stability and translation can also affect the final signal unless transcription is measured separately.
Step by step
- 1
Name DNA and protein separately
An enhancer binds an activator.
- 2
Trace the physical connection
Looping brings distant complexes into contact.
- 3
Choose a readout
RNA abundance and reporter protein are related but not identical evidence.
Worked example
Work through the evidence
Deleting an enhancer lowers reporter RNA while the promoter remains intact. Explain.
One way to explain it
The promoter can still support initiation, but loss of enhancer-bound activators reduces recruitment or activity of the transcription machinery, lowering transcription.
Why this answer works
- An enhancer affects rate rather than becoming the RNA product.
- Residual transcription does not disprove enhancer function.
Is this true? "An enhancer is a protein that attaches to DNA."
An enhancer is a DNA sequence; an activator is a protein that can bind it.