AP Syllabus focus:
‘Regulatory DNA sequences interact with regulatory proteins to control transcription, so some genes are always expressed while others are inducible.’
Gene expression is controlled largely at the level of transcription. Cells “decide” which genes to transcribe by using specific DNA regions and proteins that bind them, producing stable or flexible expression patterns.
Core idea: DNA regions + regulatory proteins control transcription
Regulatory DNA sequences (cis-acting elements)
Regulatory DNA sequences are stretches of DNA that influence transcription by serving as binding sites for regulatory proteins. They function only when located on the same DNA molecule as the gene they regulate.
Regulatory DNA sequence: A DNA segment that affects transcription of a nearby gene by binding regulatory proteins, thereby increasing or decreasing RNA polymerase recruitment and activity.
These sequences can be located:
DNA looping allows enhancer-bound transcription factors to contact the promoter-bound transcription machinery even when the regulatory DNA element is far away along the chromosome. This diagram highlights the cis-acting enhancer site, the bound transcription factor, and the promoter/RNA polymerase complex brought into proximity by looping. Source
Near the transcription start site (common for many control elements)
Far from the gene (still able to influence transcription through DNA looping in many systems)
Transcription factors and other regulatory proteins (trans-acting factors)
Regulatory proteins “read” regulatory DNA sequences and convert binding events into changes in transcription rate.
Transcription factor: A regulatory protein that binds specific DNA sequences and influences transcription, typically by promoting or blocking recruitment and function of RNA polymerase.
Transcription factors often have:
A DNA-binding domain that recognises a particular base sequence (a motif)
An activation or repression domain that interacts with other proteins involved in transcription
A single gene may integrate inputs from multiple transcription factors, allowing context-dependent control (cell type, environment, developmental stage).
How binding changes transcription output
Positive control (activation)
When an activator binds its regulatory DNA sequence, transcription commonly increases because the activator:
Helps recruit RNA polymerase to the gene
Stabilises the assembly of the transcription machinery
Promotes transition to productive RNA synthesis
Negative control (repression)
When a repressor binds its regulatory DNA sequence, transcription commonly decreases because the repressor:
Blocks RNA polymerase binding or movement
Prevents activators from functioning (competition or masking)
Recruits other proteins that reduce transcriptional activity
The key AP idea is that DNA sequence-specific binding provides selectivity: only genes with the matching regulatory sequences respond to a given transcription factor.
This schematic shows how multiple regulatory proteins bound at an enhancer communicate with promoter-bound general transcription factors and RNA polymerase II, often through mediator, to control transcription initiation. It also visualizes the spatial logic of enhancer–promoter looping that enables long-range regulation. Source
Always expressed vs inducible genes
Constitutive (often “always on”) expression
Some genes are expressed at relatively constant levels because their products are continuously needed for basic cellular function (for example, core metabolism and maintenance). This “baseline” expression pattern is supported by regulatory DNA sequences that promote steady transcription and by a cellular environment where required transcription factors are routinely available.
Inducible (regulated “as needed”) expression
Other genes are inducible, meaning their transcription changes in response to signals. Induction occurs when a signal alters transcription factor activity or availability, such as by:
Changing a transcription factor’s shape so it can bind DNA
Allowing a transcription factor to enter the nucleus
Increasing or decreasing transcription factor concentration
Inducible control is adaptive because it:
Conserves energy and resources by limiting unnecessary transcription
Allows rapid response to environmental change (nutrients, stress, signalling molecules)
Specificity and combinatorial regulation
A major principle of transcriptional regulation is combinatorial control: multiple regulatory DNA sequences and multiple transcription factors can work together to fine-tune transcription. As a result:
The same transcription factor can regulate many genes (shared binding motifs)
The same gene can respond differently depending on which transcription factors are present
Small differences in regulatory DNA sequences can change binding strength and transcription level
This interaction-based logic explains how cells with the same genome can show different expression patterns and how regulatory changes can strongly affect phenotype without changing protein-coding sequence.
FAQ
They bind short sequence motifs using structural domains (e.g., helix-turn-helix, zinc fingers) that make chemical contacts in the major groove.
Because motifs are short, context and cooperative binding with other proteins often improves specificity.
It depends on the protein domains it carries and the partners it recruits.
Activators recruit co-activators and the transcriptional machinery
Repressors recruit co-repressors or block activator/polymerase interactions
Yes. Different genes can have different arrangements and affinities of binding sites.
A transcription factor may activate one gene when partnered with a co-activator, but repress another when paired with a different regulatory protein.
A single base change can weaken or strengthen transcription factor binding.
That can shift transcription levels (too much/too little protein) without altering the protein’s amino acid sequence, sometimes producing major phenotypic effects.
Common approaches include DNA-protein binding assays and genome-wide mapping.
ChIP-based methods identify DNA fragments bound by a transcription factor in cells
Motif analysis predicts likely binding sites from sequence patterns
Practice Questions
Explain how regulatory DNA sequences and transcription factors work together to control transcription of a gene. (2 marks)
Regulatory DNA sequences are specific DNA regions that act as binding sites for regulatory proteins/transcription factors. (1)
Transcription factor binding changes transcription rate by increasing or decreasing RNA polymerase recruitment/activity (activation or repression). (1)
A gene X is expressed only when a particular extracellular signal is present. Describe how transcription factors could make gene X inducible rather than always expressed. (5 marks)
Gene X contains specific regulatory DNA sequences recognised by particular transcription factor(s). (1)
In the absence of signal, an activator may be inactive/not bound or a repressor may be bound, keeping transcription low. (1)
The signal alters transcription factor activity (e.g., conformational change, phosphorylation, ligand binding). (1)
The signal can change transcription factor localisation or abundance so it can bind regulatory DNA. (1)
Binding changes RNA polymerase recruitment/assembly, increasing transcription only when the signal is present. (1)
