Regulating Gene Expression (College Board AP® Biology): Study Guide

Introduction to regulating gene expression

• The genes expressed by a cell determine a cell's structure and function; this means that it is essential for cells to regulate their gene expression

• There are several ways in which gene expression can be regulated:

  • Regulatory proteins: proteins that bind to specific base sequences in DNA to switch gene expression on or off, e.g. transcription factors

  • Regulatory sequences: sequences of DNA to which regulatory proteins bind, e.g. promoters

  • Constitutive vs inducible genes:

    • Constitutive genes are always expressed (e.g. housekeeping genes needed for basic cell function).

    • Inducible genes are expressed only when required (e.g. enzymes in the lac operon).

  • Epigenetic changes: reversible modifications to DNA or histones, e.g.:

    • methylation of DNA: methyl groups can be added to DNA, reducing transcription rates

    • acetylation of histones: acetyl groups are added to histones, increasing transcription rates

  • Small interfering RNA (siRNA): single-stranded molecules of RNA that bind to complementary regions of mRNA, preventing them from being translated

  • Regulation and phenotype: The combination and level of gene expression determine cell and organism phenotype

    • Cell differentiation: occurs when genes for tissue-specific proteins are expressed (e.g. muscle vs nerve cells)

    • Sequential gene expression: during development, transcription factors activate cascades of genes in a set order

    • Phenotype outcomes: both the function of gene products and the amount produced influence traits

Coordinate regulation

• Regulatory sequences are stretches of DNA that control gene expression

• Their location relative to the gene(s) they control determines how they function:

  • Near the gene (cis-regulatory elements): directly influences transcription initiation

  • Upstream, downstream, or within introns: can act as enhancers or silencers

  • Grouped together: allows coordinated regulation of multiple genes

Coordinate regulation in prokaryotes – operons

• An operon is a cluster of genes under the control of a single promoter and operator

  • The regulatory sequence (operator) is directly upstream of the genes

  • Ensures all the genes in the operon are transcribed together as one mRNA, so proteins needed for the same function are made at the same time

• Prokaryotes regulate operons in inducible or repressible systems

  • Inducible operons: These are normally off and will be switched on by an inducer (e.g. lac operon activated by lactose)

  • Repressible operons: These are normally on and will be switched off when the end product is abundant (e.g. trp operon repressed by tryptophan)

Inducible system example: the lac operon

• The lac operon in bacteria controls the genes for lactose-digesting enzymes.

• It is inducible—normally off, but switched on when lactose is present

  • Components of the lac operon include:

    • Structural genes (lacZ, etc.) code for enzymes that digest lactose

    • Regulatory genes code for regulatory proteins that switch the expression of structural genes on and off

    • Regulatory sequences include the promoter (RNA polymerase binding site) and operator (repressor binding site)

  

The effect of lactose

• Without lactose:

  • The repressor binds to the operator, blocking RNA polymerase

  • Structural genes are not transcribed, and no enzymes are made

• With lactose:

  • Lactose binds to the repressor, preventing it from binding to the operator.

  • RNA polymerase transcribes the structural genes, enzymes are produced, and lactose is broken down

Repressible system example: the trp operon

• The trp operon controls enzymes for tryptophan synthesis

• It is repressible, meaning it is normally on, but will be switched off when tryptophan (trp) is abundant

  • Without tryptophan:

    • The repressor cannot bind the operator

    • RNA polymerase transcribes the structural genes, and tryptophan is produced

  • With tryptophan:

    • Tryptophan binds the repressor, enabling it to block the operator

    • RNA polymerase is prevented from transcribing, so synthesis stops and energy is conserved

Coordinate regulation in eukaryotes – shared transcription factors

• Genes are usually dispersed across different chromosomes rather than clustered

• These genes can still be coordinately regulated if they share regulatory sequences that bind the same transcription factor

  • For example, heat-shock genes all contain a similar regulatory element, and a single transcription factor activates them together during stress

• Regulatory sequences are stretches of DNA that control transcription

• They can be found:

  • Upstream (before the gene)

  • Downstream (after the gene)

  • Within introns (non-coding regions inside the gene)

• Some regulatory sequences act as enhancers: binding sites for transcription factors that increase transcription

  • Even if enhancers are far away, the DNA can loop around so that transcription factors bound at the enhancer physically touch the promoter region

  • This contact helps RNA polymerase bind to the promoter and start transcription

Comparison of coordinate regulation

Transcription factors

• Transcription factors are proteins that bind to regulatory DNA sequences (such as promoters or enhancers) to control gene expression

• Their action influences an organism’s phenotype by determining whether a gene is transcribed

Promoters and transcription factors

• Promoters are DNA sequences located immediately upstream of a gene

  • They are the binding site for RNA polymerase and mark where transcription begins

  • Every gene needs a promoter for basic transcription initiation, usually close to the transcription start site

• Transcription factors are proteins that recognise and bind to promoter (or nearby) sequences

  • They control how easily RNA polymerase can bind and therefore, regulate whether transcription starts

    • Activators help recruit or stabilise RNA polymerase binding, increasing transcription

    • Repressors/negative regulators block RNA polymerase from binding or moving along the DNA, reducing or preventing transcription

• In eukaryotes, multiple transcription factors often work together in complexes to finely tune expression; in prokaryotes, fewer factors are involved, but the principle is the same

Enhancers and transcription factors

• Enhancers are regulatory DNA sequences that increase the rate of transcription

  • Unlike promoters, they can be located far upstream, downstream, or within introns of the gene they regulate

• Transcription factors (activators) bind to enhancer sequences

  • The DNA can loop around so that these activators come into physical contact with the promoter region

  • This interaction helps recruit and stabilise RNA polymerase at the promoter, making transcription more likely to start

  • Enhancers, therefore, act as boosters, fine-tuning gene expression depending on the presence of specific transcription factors